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UNTANGLING THE WEB OF
ANTIRETROVIRAL PRICE REDUCTIONS
utw.msfaccess.org
1. Equal stature of both logos
13th Edition July 2010
Médecins Sans Frontières | July 2010
THE MSF CAMPAIGN FOR ACCESS TO ESSENTIAL MEDICINES
Eleven years ago, on the heels of Médecins Sans Frontières (MSF) being awarded the Nobel Peace Prize – and largely in response to the inequalities surrounding access to AIDS treatment between rich and poor countries – MSF launched the Campaign for Access to Essential Medicines. Its sole purpose has been to push for access to, and the development of life-saving and life-prolonging medicines, diagnostics and vaccines for patients in MSF programmes and beyond.
UNTANGLING THE WEB ONLINE!Médecins Sans Frontières’ guide to the prices of AIDS medicines is now in its 13th edition – and is also available in an online version. Stay up-to-date with the latest news on ARV prices and availability by checking:
utw.msfaccess.org
Untangling the Web of ARV Price Reductions | Please check utw.msfaccess.org �
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TABLE OF CONTENTS
BACkGROUND: ACCESS TO ANTIRETROVIRALS 3 AIDSProgressUnderSiege:TheEmergencyIsFarfromOver
4 Challenges:Second-ClassAIDSTreatment
9 OvercomingChallenges:StavingofftheSecondWaveoftheAccessCrisis
14 AIDSTreatmentDelayed,Deferred,Denied
15 Conclusion
16 QualityIssues
17 Methodology
18 HowtoReadtheDrugProfiles
DRUG PROFILES
ENTRy INHIBITORS
19 Maraviroc(MVC)
FUSION INHIBITORS
20 Enfuvirtide
INTEGRASE INHIBITORS
21 Raltegravir(RAL)
NON-NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITORS (NNRTI)
22 Efavirenz(EFV)
24 Etravirine(ETV)
25 Nevirapine(NVP)
NUCLEOSIDE & NUCLEOTIDE REVERSE TRANSCRIPTASE INHIBITORS (NRTI & NtRTI)
27 Abacavir(ABC)
29 Didanosine(ddI)
31 Emtricitabine(FTC)
32 Lamivudine(3TC)
34 Stavudine(d4T)
36 Tenofovirdisoproxilfumarate(TDF)
38 Zidovudine(AZTorZDV)
PROTEASE INHIBITORS (PI)
40 (ATV)
42 Darunavir(DRV)
44 Fosamprenavir(FPVorf-APV)
45 Indinavir(IDV)
46 Lopinavir/ritonavir(LPV/r)
48 Nelfinavir(NFV)
50 Ritonavir(rorRTV)
52 Saquinavir(SQV)
54 Tipranavir(TPV) Continued overleaf
Médecins Sans Frontières | July 2010�
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FIxED-DOSE COMBINATIONS AND CO-PACkS
55 Abacavir/lamivudine(ABC/3TC)
57 Lamivudine/stavudine(3TC/d4T)
59 Lamivudine/stavudine/nevirapine(3TC/d4T/NVP)
61 Lamivudine/stavudine+efavirenz(3TC/d4T+EFV)
62 Tenofovirdisoproxilfumarate/emtricitabine(TDF/FTC)
64 Tenofovirdisoproxilfumarate/emtricitabine/efavirenz(TDF/FTC/EFV)
66 Tenofovirdisoproxilfumarate/lamivudine(TDF/3TC)
68 Tenofovirdisoproxilfumarate/lamivudine/efavirenz(TDF/3TC/EFV)
70 Zidovudine/lamivudine(AZT/3TC)
72 Zidovudine/lamivudine/abacavir(AZT/3TC/ABC)
74 Zidovudine/lamivudine/nevirapine(AZT/3TC/NVP)
76 Zidovudine/lamivudine+efavirenz(AZT/3TC+EFV)
ANNExES 77 Annex1:SummaryofTable–AllPricesonOnePage
81 Annex2:ConditionsofOfferbyCompany
84 Annex3:Least-DevelopedCountries(LDCs)
84 Annex4:HumanDevelopmentIndex(HDI)
84 Annex5:Sub-SaharanCountries
84 Annex6:WorldBankClassificationofEconomies
85 Annex7:Bristol-MyersSquibbEligibleCountries
85 Annex8:AbbottEligibleCountries
85 Annex9:GileadEligibleCountries
86 Annex10:MerckEligibleCountries
87 Annex11:SuggestedResourcesforFurtherInformation
88 Annex12:CompanyContacts
89 Annex13:TheClintonFoundationAntiretroviralPriceList
92 References
99 Abbreviations
Contents continued
Untangling the Web of ARV Price Reductions | Please check utw.msfaccess.org �
BACkGROUND: ACCESS TO ANTIRETROVIRALS
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MSFiscurrentlysupportingcareandtreatmentformorethan154,000peoplein27countries.Bytheendof2008,atotaloffourmillionpeopleacrossthedevelopingworldwereonART.1
DeliveringARTtomillionsofpeopleindevelopingcountrieswasmadepossiblebecausetreatmentwasbroughtclosetowherepeoplelived,thepriceofmedicinescamedowndramatically,andtreatmentwassimplifiedandmademorepatient-friendly,withseveralmedicinescombinedintoonepill(knownasafixed-dosecombination,orFDC).Andinordertoaddresstheshortagesofmedicalstaffinmanycountries,tasksarebeingshifted,sothatnursesornurseaidescanperformmanyofthedutiespreviouslyreservedfordoctors.
Whiletheseachievementsrepresentimportantprogress,thecrisisisfarfromover.Untilrecentlyitwasestimatedthatalmost10millionpeopleareinimmediateneedoftreatment,atestamenttothepersistentemergency.2WiththerevisionoftheWorldHealthOrganization(WHO)guidelinesinlate20099,whichrecommend,inlinewithcurrentevidence,thattreatmentbeinitiatedearlierinapatient’sdiseaseprogression,thenumberofpatientsinneedofARTisexpectedbysometoincreasebyafurtherfivemillionto
around14millionpeople.3Thenumberofpeoplewhowillneedtreatmentby2030hasbeenprojectedtoreachasmanyas55million.4
Atthesametime,withgrowingnumbersofpatientsindevelopingcountrieshavingbeenontreatmentforfiveyearsorlonger,newchallengesareemergingtoensuretheirlong-termsurvival.Fortreatmenttobemostsuccessful,patientsneedtobemonitoredeffectivelyandhaveaccesstonewerandmorepotentdrugswhentheyinevitablydevelopresistanceorsideeffectstotheirmedicinesovertime.Butmostnewerdrugsareunaffordablebecauseofhighmonopolisticpricesandcrucialmonitoringtestsarenotadaptedforuseinresource-poorsettings.
However,theinternationalAIDSeffortisatacriticaljuncture,compromised
furtherbytheresponseofworldleaderstotheeconomiccrisis:thetwomainfundingsourcesforHIV/AIDSindevelopingcountries,theGlobalFundtoFightAIDS,TuberculosisandMalariaandtheU.S.President’sEmergencyPlanforAIDSRelief(PEPFAR),willnotbeabletosupportthetreatmentscale-upatitscurrentrategiveninsufficientdonorcommitment.TheGlobalFundisfacingasignificantfinancinggapandPEPFAR’sfundinglevelsareflat.187Barelyfouryearsafterworldleadersmetatthe2006UnitedNationsGeneralAssemblyandcommittedtouniversalaccesstoHIVprevention,treatmentandcare,politicalandfundingsupportiswaning.
ExtendingARVtreatmentindevelopingcountriestoallpeopleinneed,whileensuringpatientscansurvivewithHIVinthelong-term,willrequiremuchmoreinvestmentandpoliticalwill.
AIDS PROGRESS UNDER SIEGE: THE EMERGENCy IS FAR FROM OVER
HIV/AIDS is a lifelong disease, and although there is no cure, treatment with antiretroviral drugs (ARVs) prolongs and improves the quality of life.
AIDS treatment in developing countries began roughly a decade ago, mostly as small pilot projects and in the face of widespread scepticism about its feasibility in resource-poor settings. MSF was one of the first organisations to provide antiretroviral therapy (ART) in developing countries, starting with projects in Thailand and South Africa in 2000.152
‘�We’re�at�a�fork�in�the�road:�either�governments�summon�the�political�will�and�financial�resources�to�treat�AIDS�in�developing�countries,�or�current�funding�for�AIDS�treatment�stagnates,�which�means�patients�will�see�their�treatment�delayed,�deferred�and�denied.�It’s�a�question�of�choice:�if�they�don’t�help�us�treat�AIDS,�there�will�be�more�graves.’
Dr.�Tido�von�Schoen-Angerer,��Director�of�MSF’s�Campaign�for�Access�to�Essential�Medicines
Médecins Sans Frontières | July 2010�
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CHALLENGES: SECOND-CLASS AIDS TREATMENT
‘�The�number�of�people�
needing�HIV�treatment��
will�rise�over�the�next�
two�decades�and�so�will�
the�cost�of�treatment.�
This�is�because�better,�
more�effective�treatments�
have�come�on�the�market�
and�should�be�offered�to�
patients,�and�also�because,�
over�time,�more�people�will�
move�from�first-�to-second�
(and�later)�line�regimens,�
which�are�more�expensive.’�
The�Treatment�Timebomb�–�Report�of�the�Enquiry�of�the�UK�All�Party�Parliamentary�Group�on�AIDS�4
There is a growing disconnect between the AIDS treatment available to people in developed countries and to their counterparts in developing countries. In wealthy countries, AIDS now resembles a chronic disease, much like heart disease or diabetes, and patients generally have access to an increasing variety of treatment options once they inevitably develop drug resistance.5
©Jo
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A) Move to a less toxic and more robust first-line regimen
Incontrast,peoplelivingwithHIV/AIDSindevelopingcountrieslargelyhaveaccesstoonlyonecombinationofmedicinesthatcausessignificantsideeffects,withfewornoalternativesforwhentheirtreatmentfails.AndtheyoungestpeoplelivingwithAIDScontinuetobeanafterthought–paediatrictreatmentstilllagsbehindthatforadults,asdoesthedevelopmentofappropriateARVsforchildren.
IfpeoplelivingwithHIV/AIDSaretobegiventhesameprospectsforsurvivalwhethertheyliveindevelopingcountriesorinwealthycountries,urgentactionmustbeundertakentoensureaccess:
•toalesstoxicfirst-lineregimen;
•tosecond-andthird-linetreatmentoptions,aspatientsdevelopresistance;
•tobetterandtimelydetectionoftreatmentfailure,throughviralloadtesting;and
•topaediatricAIDStreatmentoptions,whichmustbeprioritised,togetherwiththepreventionofmother-to-childtransmissionofthevirus.
Thefirstlineofdefencetohelpslow
thepaceatwhichpatientsneedto
switchtonewer,moreexpensiveARV
treatmentregimensisarobustfirst-line
drugcombinationwithfewsideeffects.
Today,themajorityofpeopleon
theirfirst-lineofARVsinlow-and
middle-incomecountriesreceivethe
combinationoflamivudine/stavudine/
nevirapine(3TC/d4T/NVP).6Thankstogenericcompetition,thisregimennowcostsUS$67perpatientperyear(ppy)–99%lessthan10yearsago.Thisdramaticpricedropwaspossiblebecauseofcompetitionamongmultiplegenericmanufacturersincountrieswherethesedrugswerenotpatented,suchasBrazil,ThailandandIndia(seegraph1).
Notwithstandingthedramaticpricedropoverthepastdecade,usingthisstandardcombinationcomesatahighmedicalcost.Thedrugstavudine(d4T)causesserioussideeffects,someintolerable,suchasperipheralneuropathy.Itcanalsoleadtolacticacidosis,whichinrarecasescanleadtodeath.Italsocausesstigmatisationbecauseoverlong-termtreatment,patientsdevelopeasilyrecognisablefacialwasting.
Untangling the Web of ARV Price Reductions | Please check utw.msfaccess.org �
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Jun 00 Jun 02 Jun 03 Jun 06 Jul 07 Jul 08 Aug 09 Jun 10Dec 02 Dec 03 Apr 04 Jan 05 Jun 05Sept 01
US$
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6000
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Lowest Originator $10439
Lowest Originator $621
Lowest Originator $727
Lowest Originator $555
Lowest Originator $549
Lowest Originator $331
Brazil $2767
Hetero $295
Aurobindo $159Hetero $281
Cipla $132
Cipla $80 Aurobindo,Matrix & Cipla $67
Hetero $87
GRAPH �: GENERIC COMPETITION AS A CATALyST FOR PRICE REDUCTIONS. Thefallinthepriceoffirst-linecombinationsofstavudine(d4T),lamivudine(3TC),andnevirapine(NVP),since2000.
Stavudineisvirtuallynolongerusedinwealthycountries(in2006,forexample,fewerthan2%ofpatientsinSwitzerlandweretakingthedrug7).Patientsinthesecountriesareofferedbetter-toleratedalternatives,suchastenofovir(TDF)orzidovudine(AZT).Since2006,WHOhasrecommendedinitsHIV/AIDStreatmentguidelinesthattreatmentprovidersbeginmovingawayfromstavudine-basedregimensbecauseoftheirlong-termirreversiblesideeffects,towardstenofovirorzidovudine-containingregimens.8
ThiscallwasrepeatedinthelatestrecommendationsreleasedbyWHOinDecember2009forARTforHIVinadultsandadolescents,advisingcountriestodevelopaplantomovetowardstenofovirorzidovudine-basedfirst-lineregimens.9
Butuntilnow,thesignificantlyhighercostsofthesealternativeshavelargelypreventedthisswitchinmanydevelopingcountries.Better,less-toxicfirst-lineregimensarestillatbestnearlydoublethepriceofthestavudine-basedfirst-lineregimen.
However,therehasbeenanoteworthydownwardtrendinthepricesofless-toxicfirst-linecombinations.Thepriceoftenofovirhascomedownsignificantlyoverthepastfewyears,byalmost77%.ThismeansthatTDF-basedcombinationsarenownearlythesamepriceasthosecontainingzidovudine(seegraph2).Fixed-dosecombinationscontainingzidovudine(AZT/3TC/NVP)andthose
containingtenofovir(TDF/3TC/EFV)havebothfallen,by17%and59%respectivelyinthepastthreeyears.
Itisthankstogenericcompetitionthatthesepricesaresteadilycomingdown,andtheycanbeexpectedtofallfurtherasdemandincreases.Incountrieswherethedrugsarenotunderpatentorwherepatentsownerspermitsuchcompetition,theone-pill-once-a-daygenerictriplecombinationcontaining
tenofovir/lamivudine/efavirenz(TDF/3TC/EFV)isnowavailablefor$176ppy(seegraph2).Butinsomelowermiddle-incomecountries,patentownersdonotpermitaccesstogenericproducts,meaningthatcountrieshavetorelyonthe‘discounted’priceofferedbyoriginatorcompanies.Fortenofovir/emtricitabine/efavirenz(TDF/FTC/EFV),thismeansapricealmostsixtimesmoreexpensive,at$1,033ppy.
GRAPH �: THE PRICE OF NEWER, IMPROVED FIRST-LINE REGIMENS IN �0�0.Genericcompetitionhasallowednewer,improvedfirst-lineregimensrecommendedbyWHOtofallinprice,butinsomecountries,patentprotectionmeanspricesstayatunaffordablelevels.
Lowest generic price
AZT/3TC/NVP
Lowest generic price
TDF/3TC+NVP
Lowest generic price
AZT/3TC+EFV
Lowest generic price
TDF/3TC/EFV
Lowest generic price
TDF/FTC/EFV
Originator price for LMIC*
TDF/FTC/EFV
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*LMIC–Lowermiddle-incomecountries(seeannex6)
Médecins Sans Frontières | July 2010�
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concern.Butthelong-termbenefitsofpatientsbeingabletotolerateandstayontheirfirstARVcombinationlongercanoutweighthecosts.AstudyinLesothoshowedthatusingageneric
tenofovir-basedregimenresultsinbetterqualityoflifeforpatientsascomparedtoastavudine-basedregimen.10Andwhileshiftingtreatmentprogrammestoanewfirst-lineregimenbringswithitclearlogisticalchallengesontopof
costconcerns,itiscriticalthattreatmentprovidersbeginmovingawayfromstavudineashasbeendoneforexampleinZambia,Lesotho,Guyana,SouthAfricaandBotswana.
DESIGN HIV DRUGS WITH DEVELOPING COUNTRy NEEDS IN MIND
With95%ofpeoplewithHIV/AIDSlivingindevelopingcountries,itisurgentthatresearchanddevelopmenttakeintoaccounttheparticularneedsofthesepopulations.Suchconsiderationsmustbesystematicallyintegratedintotheearlystagesofthedrugdevelopmentprocess.
Overthelastthreeyears,therehavebeensignificantadvancesinHIVmedicine,whichhaveledtoanumberofnewdrugsfromolderclasses,aswellasentirelynewtherapeuticclassesbeingapprovedforuse.ThenewdrugclasseshavedifferentmechanismsofactiontotargettheHIVvirus,providingpeoplelivingwithHIV/AIDSwithadditionaltreatmentoptions.
However,sinceARVsaredevelopedprimarilyfordevelopedcountrymarkets,datarelevanttoaddressthespecificneedsofpopulationsindevelopingcountries,suchaspregnantwomenorpeoplewhoalsoneedtotakedrugsfortuberculosisduetoco-infection,isnotobtainedinclinicaltrials.Afurtherexampleisthelackofknowledgeabouttheinteractionsbetweenantimalarialsandantiretrovirals,12eventhough80%ofpeoplelivingwithHIVliveinregionswheremalariaisendemic.13
Further,thereiscurrentlynosafetyandefficacydataforchildrenforthenewdrugsetravirine,maraviroc,orraltegravir.Forotherdrugstherearelimiteddata:forefavirenz(nodataforchildrenunderthreeyears),
atazanaviranddarunavir(nodataforchildrenundersixyears).ThisdespitethefactthattheU.S.FoodandDrugAdministration(FDA)hasincludedincentivesandobligationstoencouragesubmissionofdataforpaediatricusesince199714andtheEuropeanMedicinesAgency(EMA)followedsuitinJanuary2007.15
Theneedforhigh-techmonitoringcanalsoaffecttheavailabilityofantiretrovirals.Forinstance,theentryinhibitormaravirocrequiresacomplicateddiagnostictestcostingmorethanUS$1,900–afactormakingitsuseimpracticableandunaffordableindevelopingcountrycontextswhereevensimplelaboratorymonitoringisrarelyavailable.
©P
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Untangling the Web of ARV Price Reductions | Please check utw.msfaccess.org �
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LifelongAIDStreatmentrequiresconstantaccesstonewerandmorepotentdrugregimenswhenpatientsdevelopsideeffectsorresistancetotheirmedicinesovertime.Althoughresistanceisaninevitableelementoflong-termtreatment,itcanbedelayedbyusingdrugcombinationswithfewersideeffectstofacilitateadherence,andcanbelimitedbychangingtreatmentsoonafterviralsuppressionbeginstowane.NewWHOguidelinesonsecond-linefurthersimplifyandprioritisethechoiceofregimens.
DemandfornewerAIDSdrugsisgrowingfast.InoneofMSF’slongest-runningAIDStreatmentprogrammes,inKhayelitsha,SouthAfrica,14%ofpatientsontreatmentforfiveyearsneededtoswitchtoasecond-linedrugcombinationbecauseofvirologicalfailure.24And25%ofthosepatientswhoswitchedagaindevelopedvirologicalfailuretotheirsecond-lineregimenafurthertwoyearslater.188
B) SECURE ACCESS TO SECOND- AND THIRD–LINE REGIMENS
MSF’sKhayelitshadataprovidesawindowintothegrowingneedforaccesstonewerAIDSdrugregimensacrossthedevelopingworldinthecomingyears.Assomepatientsindevelopingcountrieshavealreadydevelopedresistancetotheirsecond-lineregimen,itiscrucialtosecurefurthertreatmentoptionsessentialtolong-termsurvival.However,thepriceofnewerregimensremainsamajorbarriertoaccess.
Themostaffordablesecond-lineregimenrecommendedbynewWHOguidelinesistodaypricedat$465(seegraph3).Thisismorethanthreetimesthemostaffordableoftheimprovedfirst-lineregimensrecommendedbyWHO.
DEATH AT THE DOORSTEP: THEMBISA’S STORy
‘I’m so worried now because I don’t know what is going to happen to me,’saysThembisaMkhosana,amotheroftwowholivesinKhayelitsha,SouthAfrica.ThembisadiscoveredshewasHIV-positivein2001andbeganreceivingARTthroughMSF’sclinictwoyearslater.Sherespondedwelltotreatmentandwasabletoreturntoworkandtakecareofherchildren.
Butaftershowingsignsoftreatmentfailurebecauseofdrugresistance,
ThembisawasswitchedtoasecondsetofARVs.Againshedevelopedresistance.ThembisanowneedsathirdsetofARVstokeepheralivebutthosenewerdrugsareunaffordable.‘If there’s no such thing that can help me, I know that I’m going to die,’saysThembisa.‘And then who is going to look after my children?’
Thembisaisbutoneofmanypatientswhonowneedaccesstonewerandmorepotent,butunaffordableARVregimens.
‘What we are seeing in Khayelitsha is what we will soon see throughout Africa if there is not a focused push for urgent change,’saysDr.EricGoemaere,MedicalCoordinatorforMSFinSouthAfrica.
GRAPH �: THE TREATMENT TIME BOMB: THE IMPACT OF SWITCHING TO SECOND- AND THIRD-LINE REGIMENS ON THE PRICE OF ARV TREATMENT. Changingapatient’sregimenbecauseofsideeffectsortheemergenceofresistancemeansrelyingonnewer,patented,andthereforemoreexpensivedrugs.Thepriceofapossiblethird-lineregimenmaycostatleast23timesmorethanthemostaffordablefirst-lineregimen,andclosetoseventimesmorethanthemostaffordablesecond-lineregimen.Patientsandtreatmentprovidersareonceagainfacedwiththeprospectofdrugsbeingpricedoutofreach.
*Atthetimeofgoingtopress,thereisnoTDF/3TC+ATV+rco-pack.TheClintonFoundation-negotiatedpriceoftheindividualcomponentsofthispackagecomesto$465.CFexpectstheco-packtobeavailablebytheendof2010.Atthatstageitspriceisexpectedtodropto$425.
Lowest generic price
AZT/3TC/NVP
Lowest generic price
TDF/3TC/EFV
Best CF priceTDF/3TC+ATV+r
Best CF priceAZT/3TC+ATV+r
RAL+DVR+r + etravirine
US$
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465465*137 x3.4
first-linex23.4
second-linex7
possible third-line
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Pricecomparisonsoffirst-lines,second-linesandpossiblethird-lines
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‘�Seeing�a�patient�that�you�
have�been�treating�since�
2003,�now�failing�on�her�
second�combination,�you�
feel,�as�a�nurse,�you�are�a�
failure.�We�are�feeling�like�
our�hands�are�tied.’�
Mpumi�Mantangana,�MSF�nurse��in�Khayelitsha,�South�Africa
Médecins Sans Frontières | July 2010�
CH
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recommendationswhichforthefirsttimeraisestheneedfortreatmentoptionsafterfailureofsecond-linetherapy.Manystudiesareongoing,andthedrugslikelytohaveanti-HIVactivityinthird-lineregimensaredarunavir(boostedwithritonavir),etravirineandraltegravir.9
Becauseofpatentbarriers,genericcompetitiononthesemedicinesisseverelyhampered.UnlikewiththefirstgenerationofAIDSdrugs,patentsinkeyproducingcountriessuchasIndiapreventtheproductionofmuchmoreaffordablegenericversions:manyofthenewerARVswilllikelybeunderpatentinIndia,andseveralsuchasraltegravir,
maravirocoretravirinealreadyare.ThelackofcompetitionamonggenericmanufacturersmeansthatpricescannotbeexpectedtocomedownthewaytheydidforthefirstgenerationofARVs.
Thereisnogenericversionofetravirine,forexample.Itsmanufacturer,Tibotec,hasjustannounceda‘discounted’priceforSub-SaharanAfricaandleast-developedcountries,at$913ppy.Apotentialthird-lineregimencouldthusbeavailablefordevelopingcountriesattheprohibitivepriceof$3,204ppy(atbest,asthispriceappliestoonlyAfricaandleast-developedcountries).
Thereisnoroomforcomplacencyabouttheseprices.Formostpeoplewhoare
failingontheirsecond-linecombinationalready,thisunaffordablepricewillmeantheyalmostcertainlyonceagainfacedeath.
ItisimperativethatgovernmentsundertakemeasurestoensurethatpeopleinneedofnewerandmorepotentARVsarenotdeniedaccessbecauseofpatentbarriers.Thisincludes,butisnotlimitedto,theroutineuseofcompulsorylicensingandotherpublichealthsafeguardssetoutintheTRIPSAgreement(Trade-RelatedAspectsofIntellectualPropertyRights).TheplannedMedicinesPatentPoolforantiretroviralsisanimportantadditionalmechanismtoensurefutureavailabilityofaffordableessentialmedicines(seebox).
Whiletherehasbeenimportantprogressinscaling-uppaediatricAIDStreatmentoverthepastyear,childrencontinuetobeanafterthoughtwhenitcomestotreatmentanddevelopingappropriateandadaptedmedicinestomeettheirneeds.Furthermore,muchmoreeffortneedstobeplacedonpreventionofmother-to-childtransmission(PMTCT)ofthevirusinordertoeliminatetheseentirelyavoidableinfectionsinthefirstplace.
ThevastmajorityofchildrenwithHIV/AIDSareinfectedthroughtransmissionfromthemotherduringpregnancy,childbirthorbreastfeeding.PMTCThasbeensosuccessfulinwealthycountriesthatnearlynochildrenarenewlyinfectedwithAIDS.Butindevelopingcountries,nearly430,000newchildinfectionsoccurredin2008–atestamenttothefailuretoeffectivelyimplementsimplifiedandefficientPMTCTstrategiesthatcoulddramaticallyreducethenumberofchildinfections.16InthelatestWHOguidelineonPMTCTandinfantfeeding,moreoptionshavebeenrecommendedincludingtheprovisionoftripleARTtoallHIV-positivepregnantwomenandintroducingwaystoprotectthechildthroughoutthebreastfeedingperiod.76Thiswouldlessentheneedforpaediatrictreatment,ashasbeenseeninwealthycountries.
BecausetherearesofewchildrenwithHIV/AIDSinwealthycountries,thereisverylimitedinvestmentbythepharmaceuticalindustryintodevelopingappropriateandadaptedpaediatricARVs.
ItisnoteworthythattheavailablepaediatricFDCtabletsthatcomeindosesforvariouschildsizesareproducedmainlybygenericcompanies.
ThepriceofthepaediatricFDCd4T/3TC/NVP,at$53ppy,isfinallylower
thanthatforadults.ButthefactthatthefirstWHOprequalifiedpaediatricARVFDCbecameavailableonlyin2006,whiletheadultequivalenthasbeenavailablesince2001,reflectsthewayinwhichchildrenwithAIDSlagbehind.
C) PUT AN END TO THE NEGLECT OF CHILDREN LIVING WITH HIV/AIDS
DEVELOP SIMPLE DIAGNOSTIC AND MONITORING TOOLS FOR ADULTS AND CHILDREN
ItisvitallyimportanttobeabletodetectwhenapatientisnolongerrespondingtoART.Switchingsomeonetoanewerdrugcombinationtoolateortoosooncancompromisethetreatment’seffectiveness.
AtechnologyusedtodetecttheleveloftheAIDSvirusinpatients’blood–called‘viralload’testing–isthegoldstandard.However,itrequiresaccesstolaboratorieswithsophisticatedequipment,trainedstaffandthetransportofbloodsamples,allofwhichcanbecomplicatedorevenimpossibleinremotesettingsofpoorcountries.
Thereisanurgentneedforsimpleandeasy-to-usemonitoringteststhatcanbeusedonthespot,overcomingthesepracticalbarriers.Withoutaccesstosuchtests,manypatientsarebeingswitchedtooearlyortoolate,onlywhentheyappeartobegettingsickagainoncethevirushastakenholdanew.
Furthermore,HIV/AIDSdiagnosisininfantsisextremelydifficult.Inbabiesunder18monthsitcanonlybeconductedwiththeuseofacomplexDNA-baseddiagnostictestthatisexpensivetoconduct,alsorequiringtrainedpersonnelandaccesstosophisticatedlaboratoryequipment.Only15%ofchildrenborntomotherslivingwithHIVinlow-andmiddle-incomecountriesweretestedforHIVwithinthefirsttwomonthsoflife.6Thereisadesperateneedtodevelopasimplediagnostictestthatcanbeusedtodetectthevirusinyoungerinfantsonthespot,sothattreatmentcanbeinitiatedasearlyasnecessary.Earlyinfantdiagnosisiskeybecausewithouttreatment,halfthechildrenwilldiebeforetheageoftwo.
Untilnewtoolsexist,however,itisurgentfordonorsandtreatmentproviderstoensurethattheexistingdiagnostictechnologiesareimplementedaswidelyaspossible.
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Furthermore,ofthe22ARVsapproved
bytheU.S.FDAforadults,fivearenot
approvedforuseinchildrenandsixdo
notcomeinanypaediatricformulations.18
Whenpaediatricformulationsdoexist,
themajorityofthemcontinuetobe
ill-adaptedforuseinresource-poor
settings.Thismeanstheyeithercome
inpowderorsyrupform,withsomehaving
abittertaste,orneedingtobemixedwith
cleanwaterorrequiringrefrigeration,both
ofwhichcanbedifficulttocomebyin
manydevelopingcountrycontexts.
InApril2008,WHOrevisedits
paediatricARVtreatmentguidelines,
recommendingtheuseoftheprotease
inhibitorlopinavir/ritonavir(LPV/r)
forinfantsthathavebeenexposedto
nevirapine(NVP)directlyorthrough
theirmothers.130Thisrecommendation,
howeverjustified,meanstakinga
regimenincludinganLPV/rsyrup,which
FiercecompetitionamongmultiplegenericpharmaceuticalmanufacturersincountriessuchasIndiaandBrazil,wheremedicineswerenotpatented,iswhatbroughtthecostofAIDStreatmentdownby99%overthepastdecade,from$10,000to$67ppytoday.Indiahasthusbeencalledthe‘pharmacyofthedevelopingworld,’and,forexample,MSFsourcesmorethan80%oftheARVsusedinitsprojectsfromIndia.
AlackofpatentsinIndiaadditionallyfosteredtheproductionofFDCpills–crucialtothesimplificationoftreatmentthathasfosteredglobalscale-up–becausepatentsontheindividualcompoundsdidnotstandinthewayofcombiningthedrugs.
Butacrosstheglobe,increasedproductpatentingindevelopingcountriesisnowthreateningtheproductionofaffordable
genericversionsofnewermedicinesandthedevelopmentofbetterFDCs.InternationaltraderulesnowrequirethepatentingofmedicinesinkeyproducingcountrieslikeIndiaandBrazil,essentiallyeliminatingthekindofgenericcompetitionforthefuturethatbroughtpricesdowninthepast.
UndertheWorldTradeOrganization’sTRIPSAgreementandthe2001DohaDeclarationonTRIPSandPublicHealth,LDCsarenotrequiredtograntorenforcepatentsonpharmaceuticalsuntil2016.Thisperiodthereforeexpiresinbarelysixyears,afterwhichthesecountrieswillbefacingpatentbarriers.Considerationneedstobegiventohavethisperiodextended.
Tomorrow’sbattleforaccesstoaffordableARVswillneedtobefoughtinadifferentway.Toensurethatfundsstretchasfaraspossibletomeetthe
needs,policyactionsareneededtocontainthecostofdrugs,whileensuringqualitytreatmentforthelongterm.
ItwillrequireroutineuseofpublichealthsafeguardsinpatentlawsandofflexibilitiesintheTRIPSAgreement,andtheparticipationofpharmaceuticalcompanies–originatorandgeneric–innewmechanismstoboostaccess.
isnearly60%moreexpensivethana
liquidnevirapine-basedregimenandalso
requiresrefrigeration.
Atthesametime,thereisnoalternative
regimenoncethechildfailsthisregimen.
Thereisthusanurgentneedforthedevelopmentofchild-friendlydosesofheat-stableproteaseinhibitorsfortheyoungestpatients.Paediatricdosingstudiesforthenewer,morepotentdrugsmusturgentlybeconducted.
OVERCOMING CHALLENGES: STAVING OFF THE SECOND WAVE OF THE ACCESS CRISIS
‘�Reducing�the�costs�of�
drugs�could�enable�savings�
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life-saving�treatment�for�
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The�Treatment�Timebomb�–�Report�of�the�Enquiry�of�the�UK�All�Party�Parliamentary�Group�on�AIDS4
UNAFFORDABLE, AGAIN…
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•acountry’srighttodesignflexiblepatentlawsthatarefavourabletoaccesstomedicines;
•acountry’sright,whenessentialmedicinesarepatentedandunaffordable,toissuecompulsorylicensestoensureaccess;and
•pharmaceuticalcompaniesparticipatinginthenewMedicinesPatentPool,theinnovativemechanismrecentlyestablishedbyUNITAID.
WhileSection3(d)shouldhelpsafeguardagainstthegrantingoffrivolouspatents,thereisstillgreatconcernaboutnewerdrugs,inventedafter1995,whichcanbepatentedunderIndianlaw;severalsuchasetravirine,maraviroc,raltegraviralreadyare.
GenericproductionofthesenewerARVswillthusonlystartthroughlicensing–beitvoluntaryorcompulsory.
TheDohaDeclarationstressesthatcountrieshavetherighttodesignpatentlawsthatservetheinterestofpublichealth.
WhenIndiaamendeditspatentlawin2005,itincludedseveralkeysafeguardsincludingaprohibitiononthepatentingofinsignificantorminorimprovementsofknownmedicines.ThispartoftheIndiaPatentsActisknownasSection3(d).ItmeansthatpharmaceuticalcompaniesshouldnotbeabletoobtainpatentsinIndiaformedicinesthatarenotactualinventions,suchascombinationsorslightlymodifiedformulationsofexistingmedicines.Suchpatentapplicationsaredesignedtodelaygenericcompetitionthatcouldleadtolowerprices.
Forthefirsttime,acountrythusemphasisedstricterpatentabilitycriteriaforpharmaceuticalsandincludedprovisionsinitspatentlawstipulatingthatpatentsshouldonlybegrantedonmedicinesthataretrulynewandinnovative.
Thelawalsoallowsanyinterestedpartytoopposeapatentbeforeorafteritisgranted(‘pre-grant’and‘post-grant’oppositions).SuchoppositionshavebeenfiledinIndiabycivilsociety,patientgroupsandgenericcompaniesfromIndiaandBrazil,withthepositiveoutcomesthatseveralpatentsonkeyARVswererejectedbytheIndianpatentofficesonthegroundsthattheylackaninventivestepandfailtosatisfytherequirementsofSection3(d)ofthepatentlaw.
PUT A STOP TO FRIVOLOUS PATENTING
TheIndianPatentsAct,ifrigorouslyinterpreted,providesunderSection3(d)severalgroundsforrejectingapatentapplication,forinstanceifthepatentclaimedisonlyanewformofaknownpharmaceuticalsubstance.
In2006,theIndianpatentofficerejectedNovartis’patentapplicationforitsanti-cancerdrugimatinibmesylate(brandnameGleevec),onthegroundsthattheapplicationclaimsa‘newformofaknownsubstance’(Novartis’patentapplicationwasrelatedtoaparticularcrystalformofthesaltofimatinibmesylate).
Inessence,theIndianpatentofficewasapplyingthelaw,asapplicationsthatdonotclaimreal‘inventions’donotdeserveapatent.LikeNovartisinthisexample,manypatentapplicationsfiledbypharmaceuticalcompaniesareforanewuseofanolddrug,orsimplyforderivativesofolddrugsorcombinationsofolddrugs.
NovartislaunchedlegalproceedingschallengingtheconstitutionalityofSection3(d)ofIndia’sPatentsAct.ThispromptedMSFtolaunchthe‘DroptheCase’petitioninordertoprotectthe‘pharmacyofthedevelopingworld’.19NovartislostthiscaseinAugust2007whentheMadrasHighCourtupheldthepublichealthsafeguard.
ButNovartisisnotgivingup.HavinglostthebattletostrikedownSection3(d)ofIndia’sPatentsActalmostthreeyearsago,NovartishaslaunchedfreshlegalproceedingsinIndiatoweakenthiscriticalpublichealthsafeguard.TheSwissmultinationalpharmaceuticalcompanyhasfiledacasebeforetheIndianSupremeCourtinwhatcanbeconsideredthesecondpartoftheNovartiscase.
ThiscasewilldeterminethemannerinwhichSection3(d)willbeimplementedinIndia.
A) DESIGN FLExIBLE PATENT LAWS
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THREE DOWN; MANy MORE TO GO: OPPOSING PATENTS IN INDIA IN THE NAME OF ACCESS TO AFFORDABLE MEDICINES
Sinceearly2006,theIndianNetworkofPeopleLivingwithHIV/AIDS,theDelhiNetworkofPositivePeopleandthePositiveWomen’sNetwork,togetherwithothercivilsocietygroupsinIndiaandbeyondhavefiledpre-grantoppositionsagainstthegrantingofpatentsonARVsrecommendedbyWHOforfirst-andsecond-linetreatment.Manyoftheseoppositionshavebeenfiledonthebasisofthepatentlaw’sSection3(d),whichprevents‘evergreening’ofknownmedicines.
In2006,GlaxoSmithKlinewithdrewitspatentapplicationforthelamivudine/zidovudinefixed-dosecombination,afterPLHAnetworksfiledapre-grantopposition.InJune2008,India’spatentofficedecidednottograntBoehringerIngelheimapatentforthenevirapinepaediatricsyrupafterapre-grantoppositionwasfiled.Thissetanimportantlegalprecedentandwasfollowedbytwofurthercrucialrejectionsin2009forpatentsonthekeyARVstenofoviranddarunavir,oneofthemostexpensiveARVstoday.
Whileseveralpatentapplicationsrelatingtotenofovir,darunavirandotherkeyARVsarestillpendingbeforethepatentoffice,theserejectionsrepresentamajorvictoryforaccess,asgenericmanufacturershavetakenuptheproductionofthesemedicinesovertimeensuringthelowestpossiblepricesforthesedrugs.ThesedecisionshighlightthesuccessandimportanceofSection3(d)andoppositionproceduresinIndia’spatentlawtosafeguardpublichealth.Othercountriesinneedofaccesstoaffordableessentialdrugsshouldbuildsimilarpublichealthsafeguardsintotheirownpatentlaw.
Whendrugsarepatented,andpharmaceuticalcompaniesfailtomakepatentedmedicinesavailableandaffordabletopatientsindevelopingcountries,governmentsshouldmakeuseoftheirright,underinternationaltradelaws,toissuecompulsorylicencestoensuregenericcompetition,unlesspatentownersagreetovoluntarilylicensetheirdrugonreasonableterms.Inbothcases,royaltiesarepaidtothepatentholder.
COMPULSORy LICENSING CompulsorylicensingisoneofthepublichealthsafeguardsenshrinedintheTRIPSAgreement,whichallowsagovernmenttooverrideapatentbyissuingalicencetoathirdpartytoproduceorimportthedrug.Issuingacompulsorylicence(CL)hasproventobringpricesdowndramaticallybyopeningupthemarkettocompetitionandtherebyincreasingaccess.
ThecaseoftheCLissuedbyThailandforLPV/rinJanuary2007clearlyillustratesthis.Overthecourseofoneyear,thepriceforLPV/rinmiddle-incomecountriesdecreasedbyasmuchas75%,from$2,200ppytounder$900inThailandand$550incountriesintheClintonFoundation
Consortium.Similarly,aCLissuedbyBrazilforefavirenzinMay2007broughtthecostforthedruginBrazildownbyalmost70%.
EventhoughissuingaCLisentirelyinlinewithWTOrules,countriesthattakethesteptypicallyfaceimmensedirectandindirectretaliatorymeasuresandpressurefromdevelopedcountrygovernmentsandthepharmaceuticalindustry.ThiscanservetodiscourageothercountriesthatareconsideringissuingCLs.Inaworldinwhichmedicinesarebecomingincreasinglypatented,CLs,includingthoseforexport,willbeacriticalmechanismtohelpensurethatessentialmedicinesareaffordableenoughforpeopletoaccessthemandcountriesmustfeelsupportedintheirrighttoincreaseaccesstoneededmedicinesfortheircitizens.
Thisalsomeansrevisingthecurrentmechanismdesignedtoallowtheexportingofmedicinesunderacompulsorylicencetocountrieswhichhavenomanufacturingcapacity,andthereforecannot‘simply’issueaCLandproducetheirowngenericmedicines.Thismechanism,knownastheAugust30Decision,wasadoptedbytheWorldTradeOrganization(WTO)in2003.
Billedasan‘expeditioussolution’thatwouldopenupaccesstomedicinesformillions,theDecisionisinfactcompletelyflawed.CanadawasoneofthefirstcountriestoenshrinetheDecisioninitsnationallaw–butittookfiveyearsfromthetimetheCanadianAccesstoMedicinesRegime(CAMR)becamelawforthefirstmedicinestobeexportedfromCanadaunderCLtoreachpatientsinAfrica.
Whilethefactthatthedrugsfinallymadeitisobviouslygoodnews,it’squiteclearthataprocessthattakessolong,forjustonedrug,forjustonecountryisnotanadequateresponse.Giventheglobalsituationwhere70%ofpatientsinneedofARTstilldonothaveaccesstotreatment,thisprocedureissimplynotuptothetask.
CanadiancivilsocietyiscurrentlypushingfortheCAMRtobereformed,buttheireffortsarebeingresistedbythepharmaceuticalindustry.ReformisneededattheinternationallevelattheWTO,andanin-depthreviewwillbeheldatthenextTRIPSCouncilmeetinginOctober.189YetanumberofdevelopedcountriescontinuetoopposeanyreviewoftheAugust30Decision,insistingthereisnotenoughevidencetoshowthatthemechanismisnotworking.190
B) kEEP THE DOOR OPEN FOR COMPETITION, DESPITE PATENTS
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Whenadrugispatentedinagivencountry,thepatentholdermaychoosetograntvoluntarylicences(VL)toothermanufacturers,allowingthemtoproduceandexportthedrug.WhentheseVLsareofferedtomultipleproducerswithinamarketorinseveralcountriesandarenotrestrictiveintermsofwherethelicenseesareallowedtoexportthedrug,theycanbeausefulwaytoincreaseaccess.
However,restrictiveVLscanalsoservemerelytoextendtheoriginatorcompany’scontroloveragivenmarket,stipulatingconditionssuchaswhichsourcetheactiveingredientmustbepurchasedfrom,aswellastowhichcountriesthedrugscanbeexported.SuchrestrictiveVLsultimatelydonotleadtotheunhinderedcompetitionthatallowspatientstobenefitfromthelowestpricespossible,nordotheyincreaseaccessinallcountrieswherethemedicinesareneeded.
Asanexample,U.S.pharmaceuticalcompany,GileadSciences,offeredvoluntarylicenceagreementsfortheproductionoftenofovirtoanyinterestedgenericmanufacturerinIndiawithanumberofclauses.TheVLagreementsstipulatethatthegenericmanufacturersmustpurchasetheactivepharmaceuticalingredientfromGileaditselforfromaGileadlicensee,insteadoffromacheapersource,andthatthemanufacturersmaynotexportthedrugtoseveralmiddle-incomecountries,includingBrazilandChina.Thismeansthatwhilecompetitionamongmultiplemanufacturers(licensees)withinIndiahasbeentakingplace,Gileadmaintainscontroloverwhichcountriesareabletobenefitfromtheselowerprices,oftenkeepingitselfasthesolesuppliersourceinthesecountries.
Crucially,allthiswasestablishedbyGileadatatimewhentheirpatent
applicationontenofovirwasstillawaitingarulingfromIndia’spatentoffice.In2006,Indiancivilsocietyorganisationshadfiledpre-grantoppositionstothepatentapplicationsonthegroundsthatthedrugconsistsofapreviously-knownsubstanceandisthereforenotpatentableunderIndia’sPatentsAct.
InSeptember2009,theIndianpatentofficesubsequentlydeclinedtograntapatentfortenofovirdisoproxilandtenofovirdisoproxilfumarateandinJuly,theBrazilianpatentofficedeclinedthepatentforTDF.GileadisnowpursinganewtactictomaintainitspatentonTDFbyfilingdivisionalapplications(atypeofpatentapplicationwhichcontainsmatterfromapreviouslyfiledapplication)intheBrazilianandIndianpatentoffices.
VOLUNTARy LICENSING
STOP THE DELIBERATE CONFUSION OF qUALITy GENERIC MEDICINES AND COUNTERFEIT MEDICINES
Overthepastfewyearstherehavebeenconcertedattemptstosubjectdevelopingcountriestomuchstricterenforcementofintellectualproperty(IP)ruleswhichgobeyondtheobligationsrequiredundertheTRIPSAgreementandthreatenthecontinuedsupplyofaffordablemedicinestodevelopingcountries.Aspartofthispush,thereareproposalstointroducenewproceduresandlawsagainst‘counterfeiting’–beitasnationallegislation,asapartoffreetradeagreements(FTAs),inmultipleinternationalforasuchastheWorldHealthOrganizationortheCouncilofEurope,orintheAnti-CounterfeitingTradeAgreement.Suchinitiativesthreatentohamperorpreventthetradeinaffordablegenericmedicinesbetweendevelopingcountries.
Crucially,theuseoftheterm‘counterfeiting’differsaccordingtothecontext:inintellectualproperty
law,itreferstotheprotectionofcommercialtrademarks,yetthewayinwhichithasbeencommonlyunderstoodbymanyinpublichealth,isasareferencetofakeorfalsely-labelledmedicinalproductsthatpresentapublichealththreat.Thisconfusionhasbeenexploitedandthepublichealthconcernsaboutfakeorfalsely-labelledmedicinesusedasanargumenttopushforstricterenforcementofintellectualproperty.Notonlydothesemeasuresfailtoaddressthepublichealthproblems,buttheyalsoactivelyinterferewithandthreatenaccesstomedicines.
ThedangersofoverbroadIPprotectionareillustratedbytherecentuseofEuropeanUnioncustomsrules,whichareusedtohelpenforceEUpatentsandtrademarks.Theseruleshaveinfactpreventedthetimelyaccesstolife-savingmedicines.Severalshipmentsofgenericmedicines-includingAIDS
drugs-havebeendetainedintransitthroughEuropeancountriesbasedonallegationsofIPinfringement,eventhoughtheyarenotprotectedbyIPrightsinthecountriesofexportorimport.ThishasaffectedthesupplyofessentialmedicinesfrommanufacturersinIndiatopatientsindevelopingcountriesinAfricaandLatinAmerica.TheEUcustomsrulesshouldbeamendedtopreventthisoccurringagain.
AnotherexampleistheKenyanAnti-CounterfeitingActwhichpassedinDecember2008,andwhichusesadefinitionofcounterfeitingsowidethatitincludesallproductsthatarecopiesofpatentedgoods.Thiswouldalsocoverquality-assuredandlegally-producedgenericmedicines.TheActthushasthepotentialtoseriouslyendangeraccesstogenericmedicines,suchasthoseusedbyMSFandothertreatmentprovidersinKenya.ItiscriticalthattheActberevised.ThreepeoplelivingwithHIV,
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Company-led‘access’schemeshaveproventobeminimallyeffective.Whilemostmultinationalcompaniestodaydoofferdiscountsthroughtieredpricing,thedatacontainedinUntanglingtheWebofAntiretroviralPricesclearlyshowsthatintheabsenceofgenericcompetitors,manufacturersenjoyingamonopolisticsituationdonotreducepricessignificantlyenoughtomakemedicinesaffordablefordevelopingcountries.Also,countriesthatareclassifiedas‘middle-income’suchasBrazil,Thailand,ChinaorColombia,areoftenleftoutofthediscountschemealtogetherorareofferedonlyminimaldiscounts.Primarilythethreatoflosingapatentorhavingapatentbarrierremovediswhatmakescompaniesrespondandreduceprices.Insomecases,genericcompetitionisonlypossiblethroughgovernmentsissuingcompulsorylicences.
Thereisonewaycompaniescouldacttomakeadifferencetoimproveaccesstomedicinesinthedevelopingworld,however.TheinternationaldrugpurchasefacilityUNITAIDhasrecentlyestablishedaMedicinesPatentPoolforantiretrovirals.Insteadofhavingpatentsactasbarriers,companies,researchersoruniversitieslicensethepatentson
theirinventionstooneentity:theMedicinesPatentPool.
Inthisway,anygenericcompanythatwantstousethepatentedinventionscanseekalicencefromthepool,underpre-determinedlicensingterms,inexchangeforthepaymentofroyaltiestothepatentholder.Thelicenseecouldthenproducegenericversionsofthepatentedinventionsandexportthemtocountriescoveredbythelicence.
Inordertoensureasufficientlyattractive,largemarketforpotentialproducers,thelicencesmustbevalidforawidegeographicalareawhichincludesalldevelopingcountries.Thiswouldresultincompetitionbetweenproducers,bringingdrugpricesdown.
supportedbypublichealthgroups,
havesuccessfullyobtainedaninterim
injunctiontostopkeypartsofthe
Actbeingimplemented,pendinga
fullhearingofajudicialreview,on
thegroundsthatthenewlegislation
contravenestheir‘righttolife’
undertheKenyanConstitution.At
the63rdWorldHealthAssemblyin
May2010theKenyanMinisterof
Healthannouncedpublicallythat
theMinistryofHealthhadnotbeen
consultedonthedraftlawwhich
hashamperedeffortstoimprove
accesstomedicineinthecountry.11,22
Therehavebeenrecentencouraging
statementsfromtheKenyan
Governmentthatthislegislation
mustnotaffectaccesstomedicines.
HowevertheActhasnotyet
beenamended.
Inaworryingtrend,thereareattemptstointroducesimilarlegislationinUganda.Publichealthorganisationsthereareconcernedthatthecountry’sdraftCounterfeitGoodsBill2009mayalsothreatenaccesstogenericmedicinesifpassedinitspresentform.
Onemajorproblemthatisnotaddressedbytheuseoftheexcessivelygeneralterm‘counterfeit’,andwhichMSFteamsfaceinmanycountries,isposedbysubstandarddrugs.Thesearedrugsfromoriginatorcompaniesaswellasfromgenericproducersthatdonotmeetinternationalstandardsofqualitysetforthem.
Todatethough,thefocusoftheresponsetothesequestionshasbeenplacedonprotectingcommercialinterests,ratherthanaddressingseriouspublichealthissues.
Thishasmeantdivertingattentionfromwhatneedstobedone.
Indirectresponsetotheseconcerns,WHOmemberstatesagreedattheWorldHealthAssemblyinMay2010tosetupanintergovernmentalworkinggrouptoensureWHOtakesapublichealthperspectiveinitseffortstoensuretheavailabilityofquality,safe,efficaciousandaffordablemedicines,excludingtradeandintellectualpropertyconsiderations.Itisimportantthattheworkinggroupactsquicklytoaddresstheseissues,andthatproposalsforgreaterprotectionofcommercialintereststhatthreatenaccesstomedicinesarerejected.
Tolearnmoreaboutthefatalconfusionbetweenlegitimategenericmedicinesandillegalfakes,pleasewatchMSF’sanimationathttp://vimeo.com/11709053
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C) POOL PATENTS AND TAkE THE PLUNGE FOR AFFORDABLE TREATMENT
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‘�Donors�have�been�shifting�their�focus�from�AIDS�to�other�diseases,�where�there�is�a�sense�that�more�lives�can�be�saved�more�cheaply.�At�a�time�when�we�should�be�scaling�up�to�meet�the�AIDS�challenge,�in�other�words,�we�are�dialling�back.�In�our�global�war�on�AIDS,�the�international�community�is�on�the�verge�of�snatching�defeat�from�the�jaws�of�victory.’�
UN�Secretary�General�Ban�Ki-Moon,�14�June�2010
1. Limitingtreatmentslotsmeanschoosingwholivesordies:Becauseoffundingcuts,treatmentprovidersarebeingforcedtoturnpeopleinneedoftreatmentawayfromclinicsinsomecountries,havingbeenforcedbylackoffundstoonlyenrollnewpatientsontreatmentwhenothersdieordefault.
2.Delayingordeferringtreatmentencouragestransmission,illnessanddeath:ProvidingARTearlierletspeoplelivehealthierlives,reducestheincidenceofopportunisticinfections,anddecreasestheneedforresultingcareandhospitalisation.Italsoreducesthenumberofpeoplelosttofollow-upbeforetheystarttreatment.Withincreasingevidencethattreatmentisprevention,failingtoprovidetreatmentearlieralsoallowsthevirustospread.
3.Failingtoensureastabledrugsupplymeansviralloadshootsthroughtheroof:Reducedfundingleadstovolatilityindrugsupplies,whichcanleadtodangeroustreatmentinterruptions.WithoutthevirusbeingconstantlysuppressedthroughARVs,peoplecanrapidlyfallillagainanddie,anddrug-resistantstrainscanspread.
4.BreakingthepromiseofARTmeanspeoplewon’tcomeforwardtogettested:Peoplecameforwardtogettestedbecausetheyknewtreatmentwasavailableshouldtheytestpositive.Ifpeopleinneedtotreatmentcometobelievethisisnolongertrue,thehard-wonprogressonencouragingpeopletoknowtheirstatuswillcomeundone,withpotentiallydisastrousramifications.
5.SlowingAIDSeffortsmeansthenumberofkidsinfectedwithHIVwillrise:Children’sneedshaveconsistentlylaggedbehindadultsforAIDStreatment.Badlyneededdiagnostictestsanddrugoptionsforchildrenwillbeevenlessofapriorityinareducedfundingenvironment.ImprovedWHO-recommendedprotocolstopreventtransmissionofthevirusfrommother-to-child(PMTCT)willalsolikelyfallbythewayside,meaningtheneedlessinfectionofnewbornchildren.
6.SlowingdowntheintegrationofHIVandTBcaremeanspatientswillslipthroughthecracks:TBremainsthenumberonekillerofpeoplelivingwithHIV/AIDS,andprovidingintegratedcareforbothTBandHIV/AIDSisthemosteffectivewaytotacklethisdualepidemic.Butsuchintegrationhasonlybarelybeguninendemiccountries,andwaningsupportforHIV/AIDScarewillslowitevenfurther.
7.Choosingbetweenmaternal&childhealthorAIDSmeansmakingafalsechoice:AIDSisthemainkillerofwomenofchildbearingageandover40%ofdeathsofchildrenunderfiveyearsinsixsouthernAfricancountriesarebecauseofAIDS.AddressingAIDScreatespositiveknock-oneffectsinotherhealthareas.Morefundingshouldbeallocatedtoglobalhealthratherthanwithdrawingsupportfromoneareatofundanother.
8.Callinganendtodecentralisationofcaremeanit’shardertoreachpeopleinurgentneed:BringingAIDStreatmentclosetowherepeoplelivereachesmorepeopleinneedandlowerstherateofpatientslostto
follow-up.ThisisaparticularlyeffectivewaytoscaleupARTinareasthatarehardhitbyseverehealthworkershortages.Butwithoutsupport,itwillnotbepossibletoexpandthissuccessfulmodel.
9.Continuingtousedrugswithmoresideeffectsmeansrelegatingpatientstosecond-classcare:WHOhasrecommendedthatless-toxicdrugsbeusedinfirst-linetreatment,aspartoftheefforttoclosethetreatmentgapbetweenrichandpoorcountries.Thismeanssubstitutingstavudine,withsignificantsideeffects,fortenofovir(TDF),orzidovudine.Despitepricesfalling,thecheapestTDF-containingregimenisstillmoreexpensivethanolderalternatives.However,usingTDFdecreasesthecostofmanagingsideeffectsthroughmedicalcareand/orhospitalisation,therebyprovingmorecost-effectiveinthelongrun.Theprovisionofless-toxicmedicinescannotbeprioritisediffundsareshort.
10.Cuttingbackonfundingfortreatmentmeanssacrificinglong-termsurvival:AIDSisalifelongdiseaseandpatientsinevitablyneedtobeswitchedtonewerregimensasdrugresistancedevelopsovertime.Buttreatmentfailureisahiddenproblembecauseofalackofaffordableandaccessibleviralloadtesting.Further,newermedicinesaremuchmoreexpensive.Thismeansthatpatientsarelesslikelytobeswitchedwhennecessary,andevenlesssowhenthereisreducedfundingforAIDStreatment.
Donors are walking away from AIDS when �0 million people are still waiting for treatment. Help us stop the U-turn on AIDS. http://aids�0�0.msf.org
AIDS TREATMENT DELAyED, DEFERRED, DENIED
The past decade is testimony to the fact that treating AIDS in developing countries is feasible, saves lives and rebuilds devastated communities. But donors are now starting to shift their support away from HIV/AIDS, and MSF has seen the tangible effects this funding retreat is already having: care rationed because of limited treatment slots, treatment scale-up halted for those in urgent need, and an even more distant promise of universal access.
The decade ahead of us should not be spent undoing the hard-won advances. The AIDS funding retreat will have the following consequences:
Untangling the Web of ARV Price Reductions | Please check utw.msfaccess.org ��
CO
NC
LU
SIO
N
TheMedicinesPatentPoolhasthepotentialtohelpincreaseaccesstoARVsinthreekeyareas:
1.Byfosteringcompetitionamongmultiplemanufacturers,bringingpricesdownfornewermedicinesandincreasingaccess,itwillhelpmitigatetheimpactoftheTRIPSpatentregime,especiallyforthenewerARVspatentedinmanufacturingcountriessuchasIndiaandBrazil;
2. Itwillhelpfacilitatethecreationofneededfixed-dosecombinations,whereotherwisepatentsontheindividualdrugcompoundsstandintheway;and
3. ItwillfurtherfacilitatethedevelopmentofpaediatricARVformulationsandcombinations,byeliminatingpatentbarriersindevelopingcountries.
MéDECINS SANS FRONTIèRES IS CALLING FOR ALL PATENTS ON THE FOLLOWING ANTIRETROVIRALS (AND COMBINATIONS THEREOF) TO BE PUT IN THE MEDICINES PATENT POOL:lopinavir, ritonavir (Abbott);
nevirapine, tipranavir (BoehringerIngelheim);
atazanavir, didanosine (Bristol-MyersSquibb);
emtricitabine, GS-9350, elvitegravir, tenofovir disoproxil fumarate (Gilead);
efavirenz, raltegravir (Merck);
SPI-452 (Sequoia);
darunavir, etravirine, rilpivirine(Tibotec/Johnson&Johnson);
abacavir, fosamprenavir, lamivudine, maraviroc, S/GSK1349572 (ViiV)
Atthesametime,stepsmustbeundertakentoensurethatpeopleindevelopingcountriesarereceivingtheoptimalmonitoringandtreatmentthatsupportstheirlong-termsurvival,comparabletotheircounterpartslivingwithHIV/AIDSinwealthycountries.Thismeanssecuringaccesstoneededmonitoringtools,whileprovidingpatientsbothwitharobustfirst-lineregimenthathasfewsideeffects,aswellasensuringtherearetreatmentoptionsforwhenpatientsshowsignsofdrugresistanceandneedtoswitchtoasecond-orthird-linecombination.
Althoughpricesforcertainkeynewermedicineshavecomedownsignificantlybecauseofcompetitionamonggenericmanufacturersand
increaseddemand,overallpricesfor
newerdrugsremainunaffordablefor
developingcountriesandoutofreach
ofnationaltreatmentprogrammes.
Countriesmustbesupportedintheir
useofflexibilitiesininternationaltrade
rulestohelpbringpricesofnewer
drugsdownmoresystematicallyand
speedily.Thisisnecessarysothatthe
growingnumberofpeopleinneedof
newerandmorepotentdrugshave
immediateaccessoncetheyrequire
them.Pharmaceuticalcompanies
shouldparticipateintheMedicines
PatentPool,sothatneededformulations
canbemadeavailabletodeveloping
countriesmoreswiftlyandatmuch
moreaffordableprices.
HIV/AIDSmustcontinuetobetreatedastheemergencyitis.FundinglevelsmustbeincreasedtotakeonthemassivetaskofprovidingsustainedAIDStreatmentindevelopingcountries.Newfinancingmechanisms,suchasfinancialtransactiontaxesincludingcurrencytransactionlevies,shouldbeintroducedtohelpraisemuchneededadditionalsustainableandpredictableresources,partofwhichmustbededicatedtoglobalhealth.TheworryingtrendoftreatmentprovidersneedingtoscalebackARTatatimewhentheyshouldbescalingupmustbecounteredwithsustainedandreaffirmedcommitmentbyleadersanddonorstouniversalaccesstoHIV/AIDStreatment.
Looking back upon the first decade of AIDS treatment in developing countries shows key successes. Four million people on treatment are alive today, many of whom would have died without ARVs long ago. The case has thus been proven that AIDS treatment is entirely feasible in resource-limited settings. However, with six out of 10 people in need of treatment still not receiving it and with projections of up to 50 million people in need of treatment in roughly 20 years, it is clear that treatment scale up must occur at a faster pace.
MSFhasidentifiedalistofmedicineswhosepatentsshouldbeincludedinthepool,andalistofneededfixed-dosecombinationsthatitishopedthepoolwillhelpdeliver.However,thepoolwillbevoluntary,socrucially,thesuccessofthepatentpooldependsoncompanies’
CONCLUSION
willingnesstoincludetheirpatentsinthepoolforuseinalldevelopingcountries,andongenericmanufacturers’interestinthoselicences.WiththeFoundationentrustedwithrunningthepatentpoolnowofficiallyestablished,companieshavenoexcusesnottoact.
Continued from page 13
Médecins Sans Frontières | July 2010��
qU
AL
ITy
ISSU
ES
ReadersandpurchaserswishingtoobtainmoreinformationaboutdrugqualityarethereforeencouragedtoconsulttheWHOListofPrequalifiedMedicinalProductswhichcontainstheproductsthat‘meetunifiedstandardsofquality,safetyandefficacyforHIV/AIDS,malariaandtuberculosismedicines.’
MorecommonlyknownastheWHOprequalificationlist,theprojectwasinitiatedbytheWHOanddevelopedincollaborationwithotherUnitedNationsorganisations,principallyforprocurementbyUNagencies.TheprojectevaluatespharmaceuticalmanufacturersandproductsaccordingtoWHO-recommendedstandardsofqualityandcompliancewithGoodManufacturingPractices.
WHO’sPrequalificationProgrammeisabenchmarkfortheidentificationofqualityessentialmedicinesandhassignificantlyimprovedaccesstoqualitymedicinesoverthepastyears.Akeyfactorofsuccesshasbeenthatfinancialsupporttonationalprogrammeshasbeendependentonpurchasingmedicinesrespectingclearqualityassurancecriteria.InthistheWHOPrequalificationProgrammehasplayedanimportantrole,providingguidancetopurchasersonthequalityofmedicinesandtherebycreatingapositivemarketdynamicwheremanufacturersstrivetoreachWHOstandardsinordertocomplywithprocurementpolicies.
TheGlobalFundtoFightAIDS,TuberculosisandMalariahasrecentlychangeditsqualityassurancepolicysothatGlobalFundgrantfundsmayonlybeusedtoprocureantiretrovirals,anti-tuberculosisandanti-malarialfinishedproductsthatareeitherprequalifiedbytheWHOPrequalificationProgramme,authorisedforusebyaStringentDrugRegulatoryAuthority(SRA),orrecommendedforusebyanExpertReviewPanel(ERP).
Unfortunately,themajorityofdonorstodaydonothavesufficientqualityassurancecriteria,givingawrongsignaltomanufacturersbyremovingtheincentivetocomplywithWHOnormsandstandards,andultimatelyendangeringpatients’healthincountrieswheretheregulatorysystemremainsweak.DonorsanddrugpurchasersshouldtakeheedfromtheGlobalFund’sexampleandmakesurethattheyimplementaneffectivequalityassurancepolicyformedicinesboughtonbehalfofdevelopingcountries.
qUALITy OF DRUGS IN THE DATA PROVIDED IN UNTANGLING THE WEBManufacturerswhohaveatleastoneWHOprequalifiedantiretroviralformulationwereinvitedtoparticipateinthispublication.
ButnotalltheproductslistedinthisreporthavebeenprequalifiedbyWHOandonlysomeofthemareusedby
MSFinitsownprojects.ProductsincludedintheListofPrequalifiedMedicinalProducts(asofApril2010),includingtheonesapprovedbyHealthCanada,theEuropeanMedicinesAgency(EMA)througharticle58,U.S.FDAortentativelyapprovedbyU.S.FDA,appearinboldinthetablesofdrugprices.
PleaseconsulttheWHOwebsite(http://mednet3.who.int/prequal)forthelatestlistofprequalifiedproductsandforinformationonthestatusofdossierassessment.
qUALITy ISSUESThis report is a pricing guide, and as such does not include detailed information about the quality of the products listed. However, quality is important and price should not be the only factor determining procurement decisions.
Untangling the Web of ARV Price Reductions | Please check utw.msfaccess.org ��
ME
TH
OD
OL
OG
y
AlloriginatorcompaniesmarketingARVswereincludedinthesurvey,butthelistofgenericproducersisbynomeansexhaustive.OnlygenericcompaniesthathaveatleastoneARVlistedontheWHOListofPrequalifiedMedicinalProductsonthedateoftheinitialrequestforinformationwereincludedinthispublication.TheinitialquestionnairesweresentinthemiddleofApril2010.
Onlygenericmanufacturerswhoprovidedpricesfortheirproductsareincludedinthisdocument.AspenPharmacarewasinvitedtocontributetothispublication;however,thecompanyhaschosennottoprovideprices,andassuchwillnotbeincludedinthisdocument.Similarly,MacleodsandEmcurehavechosennottoprovideinformationforthispublication.
SOME IMPORTANT PRELIMINARy REMARkS ON THE DATA PRESENTED IN THIS REPORT:
•TheinformationonpricesgiveninthispublicationonlyrelatestoARVs.Itdoesnotincludeothercostslinkedtoantiretroviraltreatment,suchasdiagnosis,monitoringortreatmentofopportunisticinfections.Forinformationonthepricesoftheseproducts,pleasereferto‘InternationalDrugPriceIndicatorGuide’19andforpaediatricdrugs,‘Sourcesandpricesofselectedmedicinesforchildren’.20
•Themanufacturersprovidethepriceslistedinthispublication.Thepricespaidbythepurchasermightbehigherbecauseofadd-ons(suchasimporttaxesanddistributionmark-ups),ormaybelowerafternegotiations.Thedocumentshouldnotbeviewedasamanufacturer’spricelist,andprocurementagentsareadvisedtocontactmanufacturersdirectlytoconfirmprices.
METHODOLOGy
•Companiesusedifferenttradeterms(knownasincoterms).21Thesetradetermsoutlinetheresponsibilitiesofthemanufacturerandpurchaserswithregardtotransport,internationalfreightandinsurancecosts.Additionalinformationanddefinitionsofincotermscanbefoundinthe‘Abbreviations’sectionattheendofthisguide.Pricesinthepublicationhavenotbeenadjustedtoincorporatethedifferentterms.In2005,theU.S.GeneralAccountabilityOfficedemonstratedthatthesedifferencesdonotunderminetheiressentialcomparability.
•Originatorandsomegenericcompanieshavedifferenteligibilitycriteriafordifferentialpricingforcountriesandentities,meaningnotallcountriesandentitiescanaccessthepricethatismentionedinthisguide.Thedifferentcategoriesofpricesaredetailedonthedrugprofilepages.MoredetailedinformationonthedifferenteligibilitycriteriaisprovidedinAnnexes2-10.
•TheClintonFoundation’sHealthAccessInitiativenegotiatespricesforARVsanddiagnostictestswithgenericcompaniesonbehalfofnationalAIDSprogrammesincludedintheirconsortium.TheClintonFoundationhasreachedagreementswithsevenARVmanufacturerstolowerthepricesof38differentARVformulations,bothpaediatricandadult.Thecurrentpricelist,asofApril2010,canbefoundinAnnex13.
•Informationonpatentsisonlyindicativeandshouldbecheckedwithnationalauthorities.Itshouldinnowayformthebasisofaprocurementdecision.
•AstheinformationontheWHOListofPrequalifiedMedicinesisupdatedregularly,thelistshouldbeconsultedforup-to-dateinformationregardingquality.http://apps.who.int/prequal/
Questionnaires were sent to both originator and generic companies manufacturing antiretrovirals (ARVs), requesting information on prices for developing countries, restrictions that apply to each of the prices quoted (eligibility criteria), and any additional specificity applicable to the quoted prices. The data were collected up to May 2010.
NOTE:AnonlineversionofUntanglingtheWebofAntiretroviralPriceReductionslaunchedinJanuary2010.TheonlineversionreproducesthefeaturesofUntanglingtheWebinaclear,user-friendlyandfree-flowingdesign.Itisupdatedregularly.
Youcanaccessitathttp://utw.msfaccess.org
Médecins Sans Frontières | July 2010��
HOW TO READ THE DRUG PROFILES
HO
W T
O R
EA
D T
HE
DR
UG
PR
OF
ILE
S
GENERAL INFORMATION:
Generalinformationonthehistoryoftheproduct,brandname,dateofapprovalbytheU.S.FDAandrelevantWHOguidance.
TABLE ON PRICE INFORMATION – DEVELOPING COUNTRy PRICES, AS qUOTED By COMPANIES
AllpricesarequotedinUnitedStatesDollars(US$).Currencyconversionsweremadeonthedaythepriceinformationwasreceivedusingthecurrencyconvertersitewww.oanda.com.
Theannualcostoftreatmentperpatientyear(ppy)hasbeencalculatedaccordingtotheWHOdosingschedules,8multiplyingtheunitprice(onetablet,capsuleormillilitre)bythenumberofunitsrequiredforthedailydose,andby365.Thepriceofthesmallestunit(i.e.pricepercapsule,tablet,etc.)isincludedinbrackets.WherenoWHOguidelinesexistforaproduct,thedosageusedistheU.S.FDAapproveddosage.23
Pricesareroundeduptothethirddecimalforunitpriceandtothenearestwholenumberforyearlypriceperpatient.
Forpaediatrictreatments,pricesarecalculatedfora10kgchildusingrecommendeddosingbasedonweightbands,aspertheWHOtreatmentguidelines.137Thisisanestimate,astheweightofachildincreasesduringanygivenyear.Whenitwasnotpossibletocalculatethedosefora10kgchild,onlytheunitpriceisindicated.ForpaediatricFDCs,thedosagesusedforthecalculationarethoserecommendedbythePaediatricAntiretroviralWorkingGroupatWHO.137
ACCESS TO PRICE DISCOUNTS – CATEGORIES � AND �
WhenoriginatorcompaniesofferdiscountedpricesonARVs,eachappliesdifferenteligibilitycriteria.Thismeansthatacountrythatiseligibleforapricediscountfromonecompanymaybeexcludedfromthelistofeligiblecountriesbyanothercompany.Inthisdocument,theterm‘firstcategory’or‘category1’isusedtodescribethosecountriesthatareeligibleforthemostdiscountedpriceofferedbyacompany.Theterm‘secondcategory’or‘category2’isusedtodescribecountriesthatarenoteligibleforthelowestpricesreservedforcategory1countries,butareneverthelessofferedadiscountbycompanies–crucially,thisdiscountisusuallyconsiderablysmallerthanthediscountofferedtocategory1countries.
Toknowwhetheracountryiseligibleforadiscountedpriceofferedbyagivencompany,ortofindoutinwhichcategoryagivencountryisplacedbydifferentcompanies,pleaserefertotheannexes.
TheWHOListofPrequalifiedMedicinalProductsisalistofmanufacturersandsupplierswhomeetunifiedstandardsofquality,safetyandefficacyforHIV/AIDS,malariaandtuberculosismedicines.ProductsincludedintheWHOListofPrequalifiedMedicinalProductsforAntiretrovirals(asofApril2010)areinboldinthetablesofdrugprices.
ReadersandpurchaserswishingtoobtainmoreinformationaboutthequalityofARVsareencouragedtoconsulttheWHOPrequalificationProgramwebsiteasthislistisupdatedregularly(http://apps.who.int/prequal/).
TheClintonFoundation’sHIV/AIDSInitiativenegotiateswithseveralmanufacturersforreducedpricesforalmost38differentARVformulationsforcountriesintheirpooledprocurementconsortium.Manufacturerswhohaveaproductincludedinthemostrecentpriceannouncementareindicatedbya(CF)intheheaderofthetable.FurtherdetailsofthespecificsoftheproductcanbefoundinAnnex13.
PRICE CHANGES OVER TIME – CHART ON THE EVOLUTION OF THE LOWEST PRICE qUOTED FOR DEVELOPING COUNTRIES:
Thischartshowsthepriceevolutionovertime,forbothoriginatorandgenericproducts,asquotedtoMSFforthepurposeofthisdocumentsince2001.
IfagenericproductincludedintheWHOListofPrequalifiedMedicinalProductsisavailable,thegraphshowsthelowest-pricedgenericproductthatisincludedinthelist.IfnogenericproductisincludedintheWHOListofPrequalifiedMedicinalProducts,thelowest-pricedproductisconsideredinthegraph,regardlessofqualitystatus.
SPOTLIGHT ON ACCESS ISSUES – A LOOk AT PATENTS AND PAEDIATRICS
Themostsalientissuesrelatedtoaccesstoeachproductissummarisedhere.Thefocusisontheavailabilityofproducts,theiraffordabilityandtheiradaptabilityforthedevelopingworld.Specialcommenthasbeenincludedwhenappropriatewithregardtopatentsandpaediatrics.
There are separate drug profiles for each of the single antiretrovirals (ARVs), fixed-dose combinations (FDCs) and co-packs containing two or three ARVs. Each drug profile contains the following sections:
Untangling the Web of ARV Price Reductions | Please check utw.msfaccess.org ��
MARAVIROC ( MVC )M
AR
AV
IRO
C ( M
VC
)E
NT
Ry
INH
IBIT
OR
GENERAL INFORMATION
•Therapeuticclass:chemokineco-receptor5(CCR5)antagonist(entryinhibitor).
•NotcurrentlyincludedinWHOguidelines.
•Indicatedfortreatment-experiencedadultpatientsinfectedwithonlyCCR5tropicHIV-1detectablestrains,whohaveevidenceofviralreplicationandHIV-1strainsresistanttomultipleantiretroviralagents.25
•Originatorcompanyandproductbrandname:Pfizer,Selzentry.InApril2009,PfizerandGlaxoSmithKlinejointlyannouncedthecreationofViiV,anewjointventurefocusingsolelyontheR&DandcommercialisationofHIVmedicines.
•FirstapprovedbytheU.S.FoodandDrugAdministration(FDA):August2007.17
•NotincludedintheWHOModelListofEssentialMedicines(EML).26
•ThebasicpatentwasappliedforbyPfizerinDecember199927andisduetoexpirein2019.InMay2001,Pfizerappliedforanadditionalpatentmorespecificallyrelatedtocrystallinemaraviroc.28
PRICE INFORMATIONViiV was invited to contribute a price for this publication and has communicated it does not offer a reduced price for developing countries.
SPOTLIGHT ON ACCESS ISSUES
Maraviroc(MVC)isclassedasaCCR5co-receptorantagonistthattargetsthepenetrationofcellsbytheHIVvirus.Thisdrugoptionispredominatelyusedinthedevelopedworldas‘salvagetherapy’forpatientswhoarealreadyresistanttomultipledrugclasses.Notallpatientswillbenefitfromthisdrug,asonlysomeHIVvirusesusethisCCR5co-receptor.
Therecommendationisforpatientstohaveatropismtesttolookforthisco-receptorpriortotreatment.Indevelopingcountries,wherebasiclaboratorymonitoringisnotalwaysavailable,therealityofthistypeoftestingbeingavailableislimited.
Today,thistestisnotwidelyavailableandisexpensive,atapproximatelyUS$1,900.29
ViiVwasinvitedtocontributeapriceforthispublicationandhascommunicateditdoesnotofferareducedpricefordevelopingcountries.
PatentsPfizerobtainedapatentinIndiain2007.30
ThispatentblocksthemanufactureofgenericformulationsofMVCinIndia,limitingthemuch-neededcompetitionthathistoricallyhasbeenshowntoleadtopricereductions.
PfizerhasappliedforproductpatentsandpatentsforthecrystalforminBrazil,SouthAfrica,India,China,ARIPO31andOAPIcountries.32
Todate,patentsonthecrystalformhavebeengrantedinIndia,China,andARIPOandOAPIcountries.
PaediatricsThesafetyandefficacyofMVCinpatientsunder16yearsofagehavenotbeenestablished.
�0 Médecins Sans Frontières | July 2010
ENFUVIRTIDEE
NF
UV
IRT
IDE
FU
SIO
N I
NH
IBIT
OR
GENERAL INFORMATION
•Therapeuticclass:fusioninhibitor.
•NotcurrentlyincludedinWHOguidelines.
•Indicatedfortreatment-experiencedadultpatientswhohaveevidenceofviralHIV-1replicationdespiteongoingantiretroviraltherapy.33
•Originatorcompaniesandproductbrandname:RocheandTrimeris,Fuzeon.
•FirstapprovedbytheU.S.FoodandDrugAdministration(FDA):March2003.17
•NotincludedintheWHOModelListofEssentialMedicines(EML).26
•ThebasicpatentonenfuvirtidewasappliedforbyDukeUniversityinJune1994,34andisduetoexpirein2014.DukeresearchersfoundedthepharmaceuticalcompanyTrimeris,
whichbegandevelopmentofenfuvirtide(previouslycalledT-20)in1996.In1999,TrimerisenteredintopartnershipwithHoffmann-LaRochetocompletethedevelopmentofthedrug.Chironalsoownspatentsrelatedtoprocessesforproducingenfuvirtide,35whichexpiredin2005,butprotectionhasbeenextendeduntil2010insomeEuropeancountries.AlicensingagreementwasestablishedbetweenRocheandChironin2004.36
PRICE INFORMATIONRoche was invited to contribute a price for this publication and has communicated it does not offer a lower price for developing countries and is not planning to offer one in the future.
SPOTLIGHT ON ACCESS ISSUES
Enfuvirtidewasthefirstdrugdevelopedinthefusioninhibitorclass.ThenovelmechanismofactionpreventsthepenetrationoftargetcellsbytheHIVvirus.Thisnewdrugoptionispredominatelyusedinthedevelopedworldas‘salvagetherapy’forpatientswhoarealreadyresistanttomultipleantiretroviralagents.
Enfuvirtideisformulatedasaninjectionandrequiresthepatientorcaregivertolearnthetechniqueofreconstitutingpowdervialswithsterilewater.Sincethevialsareformulatedforsingleuse,itrequiresthepatientorcaregivertoaccuratelysyringeouttherequired
doseandvolume.Thisisnotadaptedforuseinresource-limitedsettings,andthecurrentpriceinthedevelopedworldofnearlyUS$25,000perpatientperyearisprohibitiveformanydevelopingcountriesthatmayhaveaneedforthisproduct.37
InBrazil,enfuvirtideisavailableat$12,812ppy.129
Rochewasinvitedtocontributeapriceforthispublicationandhascommunicateditdoesnotofferalowerpricefordevelopingcountriesandisnotplanningtoofferoneinthefuture.
PatentsTrimerisfiledforpatentsrelatedtomethodsforsynthesizingenfuvirtideindevelopingcountriessuchasChinaandBrazil,whichmayrununtil2019.38
ThepatentwasgrantedinChina.39
PaediatricsThedrugisapprovedforuseinchildrenoversixyearsofage.
Untangling the Web of ARV Price Reductions | Please check utw.msfaccess.org ��
RALTEGRAVIR ( RAL )R
ALT
EG
RA
VIR
( RA
L )
INT
EG
RA
SE
INH
IBIT
OR
GENERAL INFORMATION
•Therapeuticclass:integraseinhibitor.
•ListedintheWHOguidelineaspotentialthird-linedrug.8
•Indicatedfortreatment-experiencedadultpatientswhohaveevidenceofviralreplicationandHIV-1strainsresistanttomultipleantiretroviralagents.40
•Originatorcompanyandproductbrandname:Merck,Isentress.
•FirstapprovedbytheU.S.FoodandDrugAdministration(FDA):October2007.17
•NotincludedintheWHOModelListofEssentialMedicines(EML).26
•Worldsalesoforiginatorproduct:2009:US$752million41;2008:$361million;2007:$41million.42
•ThebasicpatentwasappliedforinOctober2002bytheInstituteforResearchinMolecularBiology(IRBM),Pomezia,Italy,oneofMerck’sresearchsites.43Thepatentisduetoexpirein2022.In2005,MerckandIRBMappliedforanotherpatentonthepotassiumsaltofRALwhichcanrunupto2025.44
PRICE INFORMATIONDeveloping country prices in US$ per patient per year, as quoted by companies. Thepriceinbracketscorrespondstothepriceofonetablet.
Dailydose
Merck
Category1countries Category2countries
Whocanaccessthisprice? Seeannex2&annex10
RAL400mgtablet 21113(1.525)
NotAvailable
SPOTLIGHT ON ACCESS ISSUES
Raltegravir(RAL)isthefirstofanewclassofdrugs(integraseinhibitors),whichhasanovelmechanismofactionandnoapparentcross-resistancewithotherARVs.
RAL,unlikemostproteaseinhibitors(PIs),doesnotrequireboostingwithritonavir(RTV).Thisnewdrugoptionwillbeveryimportantforpatientswhoaretreatment-experiencedandmayalreadyberesistanttomultipleantiretroviralagents.
InDecember2009,WHOreleasednewrecommendationswhichforthefirsttimecallforathird-linetherapy.Ashumanstudiesareongoing,thedrugslikelytohaveanti-HIVactivityinthird-lineregimensareboosteddarunavir,etravirineandraltegravir.9
Thereisnogenericraltegraviravailable.
RALpricingforcategory1countries(seeannex10)isextremelyhighandunaffordablefordevelopingcountries.RALpricingforcategory2countriesisstillunknown.InBrazil,however,raltegravirisalreadyincludedinthenationaltreatmentguidelinesandaround3,000patientsareonraltegravirinthecountry.Thecostperpatientperyearstandsat$5,870.129
PatentsMerckandIRBMappliedforpatentsinmanydevelopingcountrieswithgenericdrugmanufacturingcapacity,suchasBrazil,China,IndiaandSouthAfrica.IRBMwasgrantedapatentinIndiainDecember200745whichwillexpirein2022.
Genericcompetitiontoreducethepriceofthemedicinewillthereforeonlybepossiblethroughvoluntarylicencesissuedbythepatentholder,orthroughcompulsorylicencesissuedbythegovernment.
PaediatricsThesafetyandefficacyofRALinpatientsunder16yearsofagehavenotbeenestablished.Paediatricstudiesareongoinginchildrenfromfourweeksold.
�� Médecins Sans Frontières | July 2010
EFAVIRENZ ( EFV )E
FA
VIR
EN
Z (
EF
V )
NO
N-N
UC
LE
OSID
E R
EV
ER
SE
TR
AN
SC
RIP
TA
SE
IN
HIB
ITO
RS (
NN
RT
I )
GENERAL INFORMATION
•Therapeuticclass:non-nucleosidereversetranscriptaseinhibitor(NNRTI).
•Indicatedforfirst-andsecond-lineforadults,adolescentsandchildren.18,137
•Originatorcompaniesandproductbrandnames:Bristol-MyersSquibb(BMS),Sustiva;orMerck,Stocrin.
•FirstapprovalbyU.S.FoodandDrugAdministration(FDA):September1998.17
•Includedinthe16theditionoftheWHOModelListofEssentialMedicines(EML).26
•Worldsalesoforiginatorproduct:2009:US$1.277billion;2008:$1.149billion;2007:$956million;2006:$791million;
2005:$680million;2004:$621million;and2003:$544million.46,47,48,49,50
•ThebasicpatentonEFVwasfiledin1993byMerck,andisduetoexpirein2013.51Subsequently,Merckfiledforpatentapplicationsrelatedtocrystallizedforms,duetoexpirein2018.52
PRICE INFORMATIONDeveloping country prices in US$ per patient per year, as quoted by companies. Thepriceinbracketscorrespondstothepriceofonetablet/capsule/suspensiondose.ProductsincludedintheWHOListofPrequalifiedMedicinalProducts(asofApril2010)areinbold.
Dec 02
Dec03
May03
Feb05
Apr04
Jun06
Jun05
Jun 07
Jun 08
Dec09
Jun10
US$
pp
y
Month/Year
500
450
400
350
300
250
200
150
100
50
0
lowest originator price
generic priceEFV 600mg tablet
462
61
346
237
Dailydose
Merck
Aurobindo(CF) Cipla(CF) Hetero Matrix(CF) Ranbaxy Strides(CF)Category1countries
Category2countries
Whocanaccessthisprice?
Seeannex2&annex10 Norestrictions
EFV30mg/mlsuspension
- (0.094/ml) (0.151/ml)
EFV50mgcapsule - (0.083)
EFV50mgtablet - (0.120) (0.210) (0.083)
EFV100mgcapsule - (0.150)
EFV200mgcapsule 3 130 (0.119)
134 (0.122)
152(0.139)
118 (0.108)
EFV200mgtablet 3394 (0.360)
821 (0.750)
146 (0.133)
110 (0.100)
EFV600mgtablet 1237 ( 0.650)
657 (1.800)
73 (0.200)
79 (0.217)
82 (0.225)
61 (0.167)
91 (0.250)
62 (0.170)
(CF)TheClintonFoundationhasnegotiatedwiththismanufacturerforreducedpricesonsomeformulationsforcountriesintheirconsortium.SeeAnnex13fordetails.
Evolution of the lowest price quoted for developing countries since �00�:
AsofApril2010,thereweresevengenericsourcesofEFV600mgtabletlistedontheWHOListofPrequalifiedMedicinalProducts.Theonewiththelowestpriceisshownhere.
Since2002,theoriginatorpricehasdecreasedby32%,whilegenericpriceshavedroppedby87%.
Untangling the Web of ARV Price Reductions | Please check utw.msfaccess.org ��
EFA
VIR
EN
Z ( E
FV
)N
ON
-NU
CL
EO
SID
E R
EV
ER
SE
TR
AN
SC
RIP
TA
SE
INH
IBIT
OR
S ( N
NR
TI )
SPOTLIGHT ON ACCESS ISSUES
Efavirenz(EFV)isakeydrugforfirst-linetreatment,asitisverypotent,withonce-dailydosing,andiswell-tolerated.
Initsnew2010guidelines,WHOrecommendstheuseofEFV-incombinationwithtwoNRTIs,oneofwhichshouldbezidovudine(AZT)ortenofovir(TDF)–asapreferredfirst-lineantiretroviraltreatment.9
EFVisalsorecommendedasthepreferredNNRTIforpatientsstartingARTwhileontuberculosistreatment.Rifampicin,oneofthemaindrugsusedtotreatTB,interactswithnevirapine(NVP),resultinginlowerbloodlevelsofNVP.EFV,however,doesnothavethesamedegreeofinteraction,andcanbeusedasanalternative.
Itsprice,however,remainshigh,particularlyforcountriesincludedinMerck’ssecondpricingtier(seeannex10),wherethepriceofEFV600mgtabletexceedsbymorethan10timesthepriceofthegenericversion.
Merckphasedoutthe200mgand50mgcapsuleformulations,whichhavebeenreplacedbytablets.
Patents
GenericcompetitionfromanumberofIndianmanufacturershasbroughtthepriceofEFVdownsignificantly.However,EFVremainsexpensiveincountrieswhereMerckholdspatentsthatblocktheproductionandsaleofgenerics.
IncountrieswhereEFVispatented,governmentsandcivilsocietygroupshavetakenvariousmeasurestoensuregenericcompetitionandlowerprices,including:
•InNovember2006,ThailandissuedacompulsorylicencetoimportgenericversionsofEFVfromIndia.Asaresult,theThaigovernmentisnowpurchasingEFVatUS$106perpatientperyear(ppy),whichisconsiderablylowerthanthepreviouspriceof$511ppy.53,54
•InMay2007,Brazil,afternumerousunsuccessfulnegotiationswithMerck,issuedacompulsorylicencetoimportmoreaffordablegenericversionsofEFVfromIndia.Atthetime,thepriceofEFVinBrazilwas$580ppyandhadnotchangedsince2003.Afterthecompulsorylicence,BrazilbegantoimportagenericversionprequalifiedbyWHOfor$190ppy.InFebruary2009,thepublicmanufacturerFarmanguinhos(Fiocruz)launchedthenationalgenericversionforuseintheBrazilianhealthsystem.55
•InSouthAfrica,Merck’srefusaltoallowsufficientgenericcompetitioncontributedsignificantlytothehighpriceofthedrug.ThisledtheAIDSLawProject(ALP),actingonbehalfoftheTreatmentActionCampaign(TAC),tofileacomplaintbeforetheCompetitionCommissioninNovember2007.Asaresult,Merckrecentlyagreedtolicenseitsproducttootherproducers,openingtheopportunityforgenericcompetitioninSouthAfrica,wheresixsuppliersnowmarketefavirenzorefavirenz–containingcombinationproducts.56
•InIndia,apatentfortheprocessofpreparingform1ofcrystallineEFVwasgrantedinJune2005.57EventhoughMerckdoesnotholdaproductpatentforEFV,thisrecentlygrantedprocesspatent
appearstoprotectakeyprocessformanufacturingEFV,andcouldthereforehaveanimpactongenericproductionofEFVinIndia.ThispatenthasthereforebeenopposedbyIndiancivilsocietyorganisationsusingthepost-grantoppositionproceduresenshrinedinIndia’spatentlaw.58
Inaddition,Gilead59andBMShavefiledpatentapplicationsrelatedtocombinationsofEFVwithotherARVs.Inparticular,BMS’seffortstoreceiveapatentfortheonce-a-daypillEFV/FTC/TDF60willhaveanimpactonaccesstoimprovedfirst-lineARVtreatmentinthedevelopingworld.InIndia,thepatentofficehasalreadyrejectedGilead’sapplication,61ascombinationsofknownmoleculesarenotpatentableunderIndia’spatentlaw.
PaediatricsDespitehavingreceivedU.S.FDAapprovalforuseinadultsin1998,thereisstillnoestablisheddosingofEFVforchildrenlessthanthreeyearsofage.ThereisanurgentneedtoestablishthedosingofEFVforthisagegroup.
Inearly2008,BMS,whichmarketsEFVinEurope,discontinuedthemanufactureofthe100mgcapsule,furtherlimitingoptionsforpaediatricpatients.Theoralsolution,whileallowingmoreflexibilityindosing,mustbediscarded30daysafterbeingopened,andisnotinterchangeableonamgpermgbasiswiththesoliddosageforms.Thebioavailabilityoftheoralsolutionislessthan70%oftheoraldosageforms,andhencealargerdoseisrequiredtoobtainthesamebloodlevels.
�� Médecins Sans Frontières | July 2010
ETRAVIRINE (ETV)E
TR
AV
IRIN
E (
ET
V)
NO
N-N
UC
LE
OSID
E R
EV
ER
SE
TR
AN
SC
RIP
TA
SE
IN
HIB
ITO
RS (
NN
RT
I )
GENERAL INFORMATION
•Therapeuticclass:non-nucleosidereversetranscriptaseinhibitor(NNRTI).
•ListedintheWHOguidelineaspotentialthird-linedrug.8
•ApprovedbyU.S.FoodandDrugAdministration(FDA)fortreatment-experiencedadultpatientswhohaveevidenceofresistancetoanNNRTIandotherantiretroviralagents.62
SPOTLIGHT ON ACCESS ISSUES
InDecember2009,WHOreleasednewrecommendationswhichforthefirsttimecallfortheneedforthird-linetherapy.Asmanystudiesareongoing,thedrugslikelytohaveanti-HIVactivityinthird-lineregimensareboosteddarunavir,etravirineandraltegravir.9
EtravirinewasapprovedbytheU.S.FDAinJanuary2008,andreceivedmarketingapprovalbytheEMAinAugust2008.Ithasnotyetbeenapprovedbyanydevelopingcountryhealthauthority.However,theproductisavailablethroughapre-approvalaccessprogramwhichismanagedbyAspenPharmacare.
•Originatorcompanyandproductbrandname:Tibotec,Intelence.
•FirstapprovedbytheU.S.FDA:January2008.17
•NotincludedintheWHOModelListofEssentialMedicines(EML).26
•ThebasicpatentonetravirinewasappliedforbyJanssenPharmaceuticain1999andisduetoexpirein2019.63In2006,Tibotecappliedforsubsequentpatentsrelatedtonovelseriesofbisarylsubstitutedpyrimidinederivatives.BothJanssenPharmaceuticaandTibotecarenowpartofJohnson&Johnson.64,65
PRICE INFORMATIONDeveloping country prices in US$ per patient per year, as quoted by companies. Thepriceinbracketscorrespondstothepriceofonetablet.
ThepriceofetravirinehasnowbeenrevealedforthefirsttimebyTibotec.AtUS$913ppy,thispriceisprohibitiveforthedevelopingcountries.Thereisnogenericversionofthisdrugavailable.
PatentsPatentshavebeenappliedforwidelyinthedevelopingworld,includinginAfrica.JanssenPharmaceuticaobtainedthemoleculepatentinIndia66andChina.39
Thispatentwillblockthedevelopmentofgenericformulationsofetravirine,unlesslicences–voluntaryorcompulsory-areissuedtogenericcompaniesforthemanufactureofaffordableversionsofthedrug.
PaediatricsEtravirineisnotapprovedforuseinchildrentoday.AwaiverofpaediatricstudiesfrombirthtotwomonthswasgrantedbytheEMAongroundsthatthemedicinedoesnotrepresentsignificanttherapeuticbenefitoverexistingtreatments.67
Dailydose Tibotec
Whocanaccessthisprice? Seeannex2
ETV100mgtablet 4913(0.625)
Untangling the Web of ARV Price Reductions | Please check utw.msfaccess.org ��
NEVIRAPINE ( NVP )N
EV
IRA
PIN
E ( N
VP
)N
ON
-NU
CL
EO
SID
E R
EV
ER
SE
TR
AN
SC
RIP
TA
SE
INH
IBIT
OR
S ( N
NR
TI )
GENERAL INFORMATION
•Therapeuticclass:non-nucleosidereversetranscriptaseinhibitor(NNRTI).
•Indicatedforfirst-andsecond-lineforadults,adolescentsandchildren.8,137
•Originatorcompanyandproductbrandname:BoehringerIngelheim(BI),Viramune.
•FirstapprovalbyU.S.FoodandDrugAdministration(FDA):June1996.17
Evolution of the lowest price quoted for developing countries since �00�:
AsofApril2010,therewere10genericsourcesofNVP200mgtabletincludedintheWHOListofPrequalifiedMedicinalProducts.Theonewiththelowestpriceisshownhere.
Whileitwasapositiveresultthattheoriginatorcompanydroppeditspriceby50%in2007,thegenericpricehasdecreasedbyalmost80%since2001,andtodayisapproximately16%oftheoriginatorprice.
Oct 01
Dec 02
Jun02
Dec03
May03
Feb05
Apr04
Jun06
Jun05
Jun 07
Jun 08
Dec09
US$
pp
y
Month/Year
500
450
400
350
300
250
200
150
100
50
0Jun10
lowest originator price
generic priceNVP 200mg tablet
438
150
219
34
•Includedinthe16theditionof
theWHOModelListofEssential
Medicines(EML).26
•Worldsalesoforiginatorproduct:
2007:US$412million;2006:
$370million;2005:$386million;
2004:$378million.68,69,70,71
After2007,therearenosales
figuresquotedinthecompany’s
annualreport.
•ThebasicpatentsonNVPwereappliedforbyBIinNovember1990,andareduetoexpireinNovember2010.72BIalsoappliedforapatentonthehemihydrateformofNVP,usedinthesuspensionin1998,whichisduetoexpire2018.73Additionally,BIappliedforapatentontheextended-releaseformulationofnevirapinein2008,whichisduetoexpirein2028.74
PRICE INFORMATIONDeveloping country prices in US$ per patient per year, as quoted by companies. Thepriceinbracketscorrespondstothepriceofonetablet/suspensiondose.ProductsincludedintheWHOListofPrequalifiedMedicinalProducts(asofApril2010)areinbold.
Dailydose
BI
Aurobindo(CF) Cipla(CF) Hetero(CF) Huahai Matrix(CF) Ranbaxy(CF) StridesCategory1countries
Category2countries
Whocanaccessthisprice?
Seeannex2 Norestrictions
NVP10mg/mlsuspension
20ml380 (0.052/ml)
533 (0.073/ml)
66 (0.009/ml)
73 (0.010/ml)
NVP200mgtablet
2219 (0.300)
438 (0.600)
39 (0.054)
34 (0.046)
37 (0.050)
34 (0.047)
39 (0.054)
39 (0.053)
37 (0.050)
Continued overleaf
(CF)TheClintonFoundationhasnegotiatedwiththismanufacturerforreducedpricesonsomeformulationsforcountriesintheirconsortium.SeeAnnex13fordetails.
�� Médecins Sans Frontières | July 2010
NE
VIR
AP
INE
( N
VP
)N
ON
-NU
CL
EO
SID
E R
EV
ER
SE
TR
AN
SC
RIP
TA
SE
IN
HIB
ITO
RS (
NN
RT
I )
SPOTLIGHT ON ACCESS ISSUES
Nevirapine(NVP)isawidely-usedARV,predominatelyinfirst-lineregimens.Ithasbeenanimportantcomponentofthefixed-dosecombinationsthathavefosteredtreatmentscale-upinresource-limitedsettings.
ThepriceofNVPhasdecreaseddramaticallyoverthepastyearsasaresultofgenericcompetition.
PatentsBoehringerIngelheim(BI)hasobtainedthebasicpatentonNVPinseveraldevelopingcountries,butnopatentcouldbeobtainedincountriessuchasIndia,Brazil,ChinaorThailand,whichwerenotgrantingpatentsonmedicinesatthetime.Manydevelopingcountries,whereNVPisunderpatent,importgenericversionsofNVPbymakinguseofTRIPSflexibilities.
However,afterIndiaintroducedpatentprotectionforpharmaceuticalproductsin2005,BIappliedforapatentonthehemihydrateformofNVP,whichrelatestothepaediatricsuspension.CivilsocietygroupsinIndiafiledapre-grantoppositiontoBI’spatentapplicationinMay2006.InJune2008,thepatentapplicationontheNVPhemihydratewasrejectedbytheIndianpatentoffice,allowingforunrestrictedcompetitiononthepaediatricformulation.ThisconstitutedanimportantvictoryforIndiancivilsociety,asthiswasthefirstpatentapplicationrelatedtoaHIVmedicinetohavebeenrejectedasaresultofapre-grantoppositionprocess,inaccordancewiththe2005IndianPatentsAct.75
PaediatricsNVPisapprovedforuseandiswidely-usedinchildren.
WiththeincreasedprevalenceofTB/HIVco-infection,thereisaneedforfurtherstudiesintotheinteractionsbetweenNVPandtheTBdrugsrifampicinandrifabutininchildren.29
BIhasaNVPdonationprogrammeforthepreventionofmother-to-childtransmission(PMTCT).This,however,doesnotcovertreatmentforchildren.WhenBIannouncedareductionof50%forNVPinmid2007,itdidnotincludetheNVP10mg/mlsolution,whereapricedropwouldhavehadaconsiderableimpact.Itthereforecostsmoretotreata10kgchildwithNVPthananadult.
Genericmanufacturershavebeendevelopingtriplefixed-dosecombinationsincludingNVP,buttodayonlythreepaediatrictripleFDCsthatincludeNVPareincludedintheWHOPrequalificationListofMedicinalProducts.
AnewformulationofNVP20mgscoredtabletissuggestedbytheWHOPaediatricAntiretroviralWorkingGroupforthenewWHOPMTCTguidelinesforinfantprophylaxis.137
Nevirapine ( NVP ) continued
Untangling the Web of ARV Price Reductions | Please check utw.msfaccess.org ��
ABACAVIR ( ABC )A
BA
CA
VIR
( AB
C )
NU
CL
EO
SID
E &
NU
CL
EO
TID
E R
EV
ER
SE
TR
AN
SC
RIP
TA
SE
INH
IBIT
OR
S ( N
RT
I & N
tRT
I )
GENERAL INFORMATION
•Therapeuticclass:nucleosidereversetranscriptaseinhibitor(NRTI).
•Indicatedforfirst-andsecond-line:foradults,adolescentsandchildren.8,137
•Originatorcompany,andproductbrandname:GlaxoSmithKline(GSK),Ziagen.InApril2009,PfizerandGSKjointlyannouncedthecreationofViiV,anewjointventurefocusingsolelyontheR&DandcommercialisationofHIVmedicines.
Evolution of the lowest price quoted for developing countries since �00�:
AsofApril2010,therewerefourgenericsourcesofABC300mgtabletincludedintheWHOListofPrequalifiedMedicinalProducts.Theonewiththelowestpriceisshownhere.
Since2001,theoriginatorpricehasdecreasedby68%,whilethegenericpricehasdecreasedby92%.
•FirstapprovalbyU.S.FoodandDrugAdministration(FDA):December1998.17
•Includedinthe16theditionoftheWHOModelListofEssentialMedicines(EML).26
•Worldsalesoforiginatorproductfor2009:US$160million;2008:$175million;2007:$215million;2006:$230million;2005:$268million;2004:$290million.77,78,79,80,81,82
•ThebasicpatentsonABCwereappliedforbyGSKin198983and1990,83andtheseareduetoexpirein2009and2010,respectively.GSKsubsequentlyappliedforanadditionalpatentsrelatedtonewintermediatesin1995,84toonthehemisulfatesaltofABCin199885andtocompositionsofABCparticularlyrelevantforpaediatricusein1999,which 86areduetoexpirein2015,2018and2019,respectively.
Oct 01
Dec 02
Jun02
Dec03
May03
Feb05
Apr04
Jun06
Jun05
Jun 07
Jun 08
Dec09
Jun10
US$
pp
y
Month/Year
3000
2500
2000
1500
1000
500
0
lowest originator price
generic priceABC 300mg tablet
438
207
1387
2628
Continued overleaf
PRICE INFORMATIONDeveloping country prices in US$ per patient per year, as quoted by companies. Thepriceinbracketscorrespondstothepriceofonetablet/doseoforalsolution.ProductsincludedintheWHOListofPrequalifiedMedicinalProducts(asofApril2010)areinbold.
Dailydose
ViiV Aurobindo(CF) Cipla(CF) Hetero(CF) Matrix(CF) Ranbaxy Strides
Whocanaccessthisprice?
Seeannex2 Norestrictions
ABC20mg/mloralsolution
10ml 230 (0.063/ml)
212 (0.058/ml)
113 (0.031/ml)
ABC60mgtablet 4 153 (0.105)
134(0.092)
183 (0.125)
540(0.370)
ABC300mgtablet 2 438 (0.600)
243 (0.333)
207 (0.283)
256(0.350)
219 (0.300)
274 (0.375)
(CF)TheClintonFoundationhasnegotiatedwiththismanufacturerforreducedpricesonsomeformulationsforcountriesintheirconsortium.SeeAnnex13fordetails.
�� Médecins Sans Frontières | July 2010
AB
AC
AV
IR (
AB
C )
NU
CL
EO
SID
E &
NU
CL
EO
TID
E R
EV
ER
SE
TR
AN
SC
RIP
TA
SE
IN
HIB
ITO
RS (
NR
TI
& N
tRT
I )
SPOTLIGHT ON ACCESS ISSUES
InDecember2009,WHOreleasednewrecommendationsforantiretroviraltherapyforHIVinadultsandadolescents.Forsecond-linetreatment,proteaseinhibitorssuchasritonavir-boostedatazanavir(ATV/r)orlopinavir(LPV/r),andsimplifiedNRTIoptionsarerecommended.Abacavir(ABC)anddidanosine(ddI)arenolongerrecommendedasoneoftheNRTIbackbonesinsecond-linetherapy.9
EventhoughthepriceofABChasfallenbyalmost92%ingenericpricingsince2001,thecurrentlowestgenericpriceismorethantwicethelowestpriceoftenofovir(TDF)orzidovudine(AZT).Additionally,GSK’sdifferentialpricingstructure(seeannex2)excludessomelow-andmiddle-incomecountriesthatarenotfundedbytheGlobalFund.Thecurrentpriceinthedevelopedworldof$4,600ppyisprohibitiveformanydevelopingcountriesthatneedtoaccesstheproduct.87
PatentsThepriceofABCdecreasedsignificantlywiththearrivalofgenericcompetition.SuchcompetitionwasmadepossiblebecauseGSKcouldnotapplyforthebasicpatentsonABCincountrieswithgenericproductioncapacitysuchasIndia,whichdidnotgrantpatentsonpharmaceuticalsatthetime.
However,patentshavebeengrantedinChina39,andGSKhasappliedforpatentsonthehemisulfatesaltofABCandoncompositionsofABCparticularlyrelevantforpaediatricuseinIndia.GSKwithdrewitspatentapplicationonthehemisulfatesaltofABCinOctober2007afteritwasopposedbycivilsocietygroupsinJuly2006inapre-grantoppositionprocedure.88Nevertheless,thepatentmorespecificallyrelatedtopaediatricformulationswasgrantedinDecember2007.89ThispatentraisesconcernsoverthecontinuedgenericavailabilityoftheABCpaediatricformulation,whichisanimportantoptionforyoungchildrenwithHIV/TBco-infection.
PaediatricsABCisapprovedforuseinchildren.
Thereisaliquidformulationandtoday,twogenericsourcesofpaediatricABC60mgtabletareincludedintheWHOListofPrequalifiedMedicinalProducts.
ABCwillcontinuetobeanimportantdrugforHIV/TBco-infectedsmallchildren,whohavelimitedchoicesofARVsbecauseofdruginteractionsbetweenTBdrugsandnevirapine(NVP),andbecauseofthelackofdosagedataonefavirenz(EFV)forchildrenunderthree.
Today,once-dailydosingofABCisonlyrecommendedforpatientsover12yearsofage;morestudiesareneededtoconfirmthesafetyofdailydosingofABCinchildren.90
Abacavir ( ABC ) continued
Untangling the Web of ARV Price Reductions | Please check utw.msfaccess.org ��
DIDANOSINE ( ddI )D
IDA
NO
SIN
E ( d
dI )
NU
CL
EO
SID
E &
NU
CL
EO
TID
E R
EV
ER
SE
TR
AN
SC
RIP
TA
SE
INH
IBIT
OR
S ( N
RT
I & N
tRT
I )
GENERAL INFORMATION
•Therapeuticclass:nucleosidereversetranscriptaseinhibitor(NRTI).
•Indicatedforsecond-lineforchildren.137
•Originatorcompanyandproductbrandname:Bristol-MyersSquibb(BMS),Videx/VidexEC.
•FirstapprovalbyU.S.FoodandDrugAdministration(FDA):October1991forchewabletablets;October2000forenteric-coatedcapsules.17
•Includedinthe16theditionoftheWHOModelListofEssentialMedicines(EML).26
•Worldsalesoforiginatorproduct:2005:US$174million;2004:$274million;2003:$354million.After2005,therearenosalesfigureslistedinthecompany’sannualreport.49
•ThebasicpatentonddIfiledin1985bytheNationalInstitutesofHealth(NIH),aU.S.governmentresearchinstitute,hasexpired,butBMSholdspatentsonimprovedformulationsinsomecountries,whichrununtil2012and2018.91
PRICE INFORMATIONDeveloping country prices in US$ per patient per year, as quoted by companies. Thepriceinbracketscorrespondstothepriceofonetablet/capsule/doseoforalsolution.ProductsincludedintheWHOListofPrequalifiedMedicinalProducts(asofApril2010)areinbold.
Dailydose
BMS
Aurobindo Cipla RanbaxyCategory1countries
Category2countries
Whocanaccessthisprice? Seeannex2&annex7 Norestrictions
ddl2gpowderforreconstitution(finalconcentration10mg/ml)
12ml 276 (12.590/2g)
308 (14.057/2g)
88 (4.000/2g)
ddl25mgtablet 5 212 (0.116)
429 (0.235)
115(0.063)
228(0.125)
ddl50mgtablet - (0.158) (0.235) (0.079) (0.115)
ddl100mgtablet 4 311 (0.213)
364 (0.249)
194 (0.133)
188(0.129)
242(0.166)
ddl125mgenteric-coatedcapsule 1 110 (0.300)
ddl150mgtablet - (0.308) (0.345) (0.225) (0.167)
ddl200mgtablet - (0.267) (0.257)
ddl200mgenteric-coatedcapsule - (0.383)
ddl250mgenteric-coatedcapsule 1 223 (0.611)
249 (0.683)
170 (0.467)
103(0.283)
ddl400mgenteric-coatedcapsule 1 288 (0.789)
322 (0.881)
256 (0.700)
132(0.363)
Continued overleaf
�0 Médecins Sans Frontières | July 2010
Dec03
May03
Feb05
Apr04
Jun06
Jun05
Jun 07
Jun 08
Dec09
US$
pp
y
Month/Year
350
300
250
200
150
100
50
0Jun10
268
lowest originator price
generic priceddI EC 400mg capsule
288270271
DID
AN
OSIN
E (
dd
I )
NU
CL
EO
SID
E &
NU
CL
EO
TID
E R
EV
ER
SE
TR
AN
SC
RIP
TA
SE
IN
HIB
ITO
RS (
NR
TI
& N
tRT
I )
SPOTLIGHT ON ACCESS ISSUES
InDecember2009,WHOreleasednewrecommendationsforantiretroviraltherapyforHIVinadultsandadolescents.Forsecond-linetreatment,proteaseinhibitorssuchasritonavir-boostedatazanavir(ATV/r)orlopinavir(LPV/r),andsimplifiedNRTIoptionsarerecommended.Abacavir(ABC)anddidanosine(ddI)arenolongerrecommendedasoneoftheNRTIbackbonesinsecond-linetherapy.9
BMS’sdifferentialpricingstructurelimitsthepricesquotedabovetosub-SaharanAfricaandlow-incomecountries.ThisstructureleavessomecountriespayingmorethanUS$3,600perpatientperyearforddI400mgenteric-coated(EC)capsules,whichisprohibitiveformanyofthesecountries.87
In2007,BMSannounceditsplanstorestructurethecompanyintoaBioPharmacompany.Theplansincludereducingthenumberofbrandsinthecompany’smatureproductsportfolioby60%between2007and2011andreducingofthecompany’smanufacturingfacilitiesbymorethan50%bytheendof2010.92Asaresult,BMShas
takenadecisiontocloseitsmanufacturingplantinMeymac,France,inJune2010whichmightaffecttheavailabilityofsomeantiretroviralsforthedevelopingworlduntilthenewproductionplantintheU.S.isabletoproducethoseformulationsagain.In2006,BMSdiscontinuedthesaleofthechewable/dispersiblebufferedtabletsintheU.S.Theenteric-coatedcapsulesaremoreadaptableastheycanbetakenoncedailyand,unlikethetablets,donotcontainabuffer.Thebufferhasbeenassociatedwithstomachupsetsandabitterandchalkytaste.
InDecember2009,BMSdiscontinuedthesaleandmanufacturingofddI200mgtabletgloballyduetolowdemandfortheproduct.
Today,fourgenericddIECformulationsareincludedintheWHOListofPrequalifiedMedicinalProducts.
Patents
Thepatentonenteric-coatedcapsuleswasgrantedinBrazil,China,andARIPOandOAPIcountries.Noapplicationclaimingapatentonenteric-coated
capsuleshasbeenpublishedinIndia,allowingagenericversiontobelaunched.However,wherethepatenthasbeengrantedinotherdevelopingcountries,theimportationofthemoreaffordableversionfromIndiaisblocked.
Paediatrics
Foryoungerchildren,theonlyoptionsarebufferedtabletsthatcomewithahighpillburden,ortheddIpowderforreconstitution,whichrequiresmultipledilutions,firstwithwaterandthenwithanantacid,toobtainthefinalconcentration.Oncereconstituted,thesolutionmustberefrigeratedandmustbediscardedafter30days.
BMSoffersnodifferentialpricefortheddIEC125mg,whichisthebest-adaptedoptionforolderchildrenwhocanswallow.
DuetotheimminentclosureoftheBMSfacilityinMeymac,France,inJune2010,aserioussupplyproblemfordidanosine25mgand50mgtabletsofwhichthereisnoWHOprequalifiedgenericsource,islikelytoemerge.
Evolution of the lowest price quoted for developing countries since �00�:
AsofApril2010,therewasonegenericsourceofddI400mgenteric-coatedcapsuleincludedintheWHOListofPrequalifiedMedicinalProducts.Itspriceisshownhere.
Didanosine ( ddI ) continued
Untangling the Web of ARV Price Reductions | Please check utw.msfaccess.org ��
EMTRICITABINE (FTC)E
MT
RIC
ITA
BIN
E ( F
TC
)N
UC
LE
OSID
E &
NU
CL
EO
TID
E R
EV
ER
SE
TR
AN
SC
RIP
TA
SE
INH
IBIT
OR
S ( N
RT
I & N
tRT
I )
GENERAL INFORMATION
•Therapeuticclass:nucleosidereversetranscriptaseinhibitor(NRTI).
•Indicatedforfirst-andsecond-lineforadultsandadolescents.8
•Originatorcompanyandproductbrandname:Gilead,Emtriva.
•FirstapprovalbyU.S.FoodandDrugAdministration(FDA):July2003.17
•Includedinthe16theditionoftheWHOModelListofEssentialMedicines(EML).26
•Worldsalesoforiginatorproduct:2009:US$28million;2008:$31million;2007:$32million;2006:$36million;2005:$47million;2004:$58million.93,94,95,96
•ThebasicpatentonFTCandlamivudine(3TC)wasfiledbyIAFBiochemin1990andisduetoexpirein2010.AsthemolecularstructureofFTCand3TCareverycloselyrelated,thesamepatentcoversboththesedrugs.97,98
•EmoryUniversityalsoappliedforaseriesofpatentsthatrelatetoFTCbetween1990and1992.99,100Theseareduetoexpirebetween2010and2012.In2005,GileadacquiredtheroyaltyinterestforFTCundera$525millionagreementwithEmoryUniversity.101
PRICE INFORMATIONDeveloping country prices in US$ per patient per year, as quoted by companies. Thepriceinbracketscorrespondstothepriceofonecapsule.ProductsincludedintheWHOListofPrequalifiedMedicinalProducts(asofApril2010)areinbold.
SPOTLIGHT ON ACCESS ISSUES
Emtricitabine(FTC)producedbyGileadisnotofferedaspartofthecompany’sAccessProgramandisalsoneitherregisterednormarketedindevelopingcountries.Itis,however,availableinco-formulationwithtenofovir(TDF)andefavirenz(EFV).
AccordingtotheWHOtreatmentguidelines,‘FTCisanequivalentalternativetolamivudine(3TC)asitisstructurallyrelatedto3TC,sharesthesameefficacyagainstHIVandhepatitisBvirus(HBV)andhasthesameresistanceprofile.’8
ThenewWHO2010guidelinesrecommendusingTDFwitheitherFTC-or3TC-containingantiretroviralregimensinallHIV/HBVco-infectedindividualsneedingtreatment.9
PatentsAlthoughbasicpatentsonFTCcouldnotbeappliedforinIndiabecausethecountrydidnotgrantpatentsonpharmaceuticalsatthetime,GileadreportedholdingpatentrightsonFTCin45otherdevelopingcountries.102
Inmid2006,Gileadsignedlicensingagreementswith10genericmanufacturersinIndia,allowingthemtomanufactureandexportgenericversionsofGilead’sTDFincombinationwithotherARVs–includingFTC–toalimitedlistofcountries,inreturnforthepaymentofa5%royalty.103
PaediatricsFTCisapprovedforuseinchildrenandhastheadvantageofonce-dailydosing.
ThepaediatricformulationproducedbyGileadisasolutionthatrequiresrefrigerationpriortodispensingandmustbeusedwithinthreemonthsandstoredattemperaturesbelow25°C.Thisisnotadaptedtodevelopingworldneeds.
Dailydose Aurobindo Matrix
Whocanaccessthisprice? Norestrictions
FTC200mgcapsule 1 63 (0.173)
79 (0.217)
�� Médecins Sans Frontières | July 2010
GENERAL INFORMATION
•Therapeuticclass:nucleosidereversetranscriptaseinhibitor(NRTI).
•Indicatedforfirst-andsecond-lineforadults,adolescentsandchildren.8,137
•Originatorcompanyandproductbrandname:GlaxoSmithKline(GSK),Epivir.InApril2009,PfizerandGSKjointlyannouncedthecreationofViiV,anewjointventurefocusingsolelyontheR&DandcommercialisationofHIVmedicines.
LAMIVUDINE ( �TC )L
AM
IVU
DIN
E (
�T
C )
NU
CL
EO
SID
E &
NU
CL
EO
TID
E R
EV
ER
SE
TR
AN
SC
RIP
TA
SE
IN
HIB
ITO
RS (
NR
TI
& N
tRT
I )
•FirstapprovalbyU.S.FoodandDrugAdministration(FDA):November1995.17
•Includedinthe16theditionoftheWHOModelListofEssentialMedicines(EML).26
•Worldsalesoforiginatorproduct:2009:US$197million;2008:$225million;2007:$309million;2006:$398million;2005:$398million;2004:$549million.104,80,81,82
•Thebasicpatentonemtricitabine(FTC)and3TCwasfiledbyIAFBiochemin1990andisduetoexpirein2010.AsthemolecularstructureofFTCand3TCareverycloselyrelated,thesamepatentcoversboththesedrugs.97
•GSKobtainedalicensefromIAFtomanufacture3TCandfiledadditionalpatentsonnewformsof3TCin1992,whichareduetoexpirearound2012.105
•GSKalsoappliedforanewformulationpatentin1998.ThispatentwasgrantedinBrazil,ChinaandinARIPOcountries.106
PRICE INFORMATIONDeveloping country prices in US$ per patient per year, as quoted by companies. Thepriceinbracketscorrespondstothepriceofonetablet/doseoforalsolution.ProductsincludedintheWHOListofPrequalifiedMedicinalProducts(asofApril2010)areinbold.
Dailydose
ViiV Aurobindo(CF) Cipla(CF) Hetero(CF) Matrix Ranbaxy(CF) Strides
Whocanaccessthisprice? Seeannex2 Norestrictions
3TC10mg/mloralsolution
10ml 84 (0.023/ml)
29 (0.008/ml)
37 (0.010/ml)
37(0.010/ml)
3TC150mgtablet 2 64 (0.087)
34 (0.047)
35 (0.048)
33 (0.045)
34 (0.046)
34 (0.047)
37 (0.050)
3TC300mgtablet 1 24 (0.067)
41(0.113)
38 (0.103)
34 (0.092)
Evolution of the lowest price quoted for developing countries since �00�:
AsofApril2010,therewereninegenericsourcesof3TC150mgtabletincludedintheWHOListofPrequalifiedMedicinalProducts.Theonewiththelowestpriceisshownhere.
Thepriceoftheoriginatorproducthasfallenby73%since2001,whilegenericpriceshavedroppedby64%.
Oct 01
Dec 02
Jun02
Dec03
May03
Feb05
Apr04
Jun06
Jun05
Jun 07
Jun 08
Dec09
US$
pp
y
Month/Year
250
200
150
100
50
0Jun10
lowest originator price
generic price3TC 150mg tablet
91
33
64
234
(CF)TheClintonFoundationhasnegotiatedwiththismanufacturerforreducedpricesonsomeformulationsforcountriesintheirconsortium.Seeannex13fordetails.
Untangling the Web of ARV Price Reductions | Please check utw.msfaccess.org ��
SPOTLIGHT ON ACCESS ISSUES
Lamivudine(3TC)isawidely-usedARVbothinfirst-andsecond-lineregimens.Ithasbeenanimportantcomponentoffixed-dosecombinationsthathavefosteredtreatmentscale-upinresource-limitedsettings.
AccordingtotheWHOtreatmentguidelines,‘FTCisanequivalentalternativetolamivudine(3TC)asitisstructurallyrelatedto3TC,sharesthesameefficacyagainstHIVandhepatitisBvirus(HBV)andhasthesameresistanceprofile.’8
ThenewWHO2010guidelinesrecommendusingTDFwitheitheremtricitabineor3TC-containingantiretroviralregimensinallHIV/HBVco-infectedindividualsneedingtreatment.9
LA
MIV
UD
INE
( �T
C )
NU
CL
EO
SID
E &
NU
CL
EO
TID
E R
EV
ER
SE
TR
AN
SC
RIP
TA
SE
INH
IBIT
OR
S ( N
RT
I & N
tRT
I )
PatentsAsthegraphillustrates,thepriceof3TCdecreaseddramaticallyaftertheonsetofgenericcompetition.Genericcompetitionfor3TCoriginatedincountrieswithmanufacturingcapacitywherethedrugisnotunderpatent,suchasIndia,ThailandandBrazil.
InChina,whereGSKstillownsexclusiverightson3TC,thepriceofthemedicineremainsveryhigh,ataroundUS$1,780perpatientperyear.GSKisusingitsmonopolyrightstoblocklocalproductionorimportationofmoreaffordablegenericversionsof3TC.
Paediatrics
3TCisapprovedforuseandiswidelyusedinchildren.
Genericmanufacturershavebeendevelopingbothdoubleandtriplefixed-dosecombinationscontaining3TC.AsofApril2010therewerefourpaediatrictripleFDCscontaining3TCincludedintheWHOListofPrequalifiedMedicinalProducts.
Today,once-dailydosingof3TCisonlyrecommendedforpatientsover16;morestudiesareneededtoconfirmthesafetyofdailydosingof3TCinchildren.90
�� Médecins Sans Frontières | July 2010
GENERAL INFORMATION
•Therapeuticclass:nucleosidereversetranscriptaseinhibitor(NRTI).
•Indicatedforfirst-lineforchildrenandalsorecommendedtomoveawayfromd4Tfirst-lineinadultsandadolescents.8,137
•WHOupdatedthe2006guidelinestorecommendareductionindoseofd4T40mgtod4T30mgforallweightcategoriesofpatients.107
•Originatorcompanyandproductbrandname:Bristol-MyersSquibb(BMS),Zerit.
•FirstapprovalbyU.S.FoodandDrugAdministration(FDA):December1994.17
STAVUDINE ( d�T ) ST
AV
UD
INE
( d
�T
)N
UC
LE
OSID
E &
NU
CL
EO
TID
E R
EV
ER
SE
TR
AN
SC
RIP
TA
SE
IN
HIB
ITO
RS (
NR
TI
& N
tRT
I )
•Includedinthe16theditionWHOModelListofEssentialMedicines(EML).26
•Worldsalesoforiginatorproduct:2006:US$155million;2005:$216million;2004:$272million;2003:$354million.After2006,therearenosalesfigureslistedinthecompany’sannualreport.108,49
•d4TwastheresultofU.S.publicsectorresearch.ItwasoriginallysynthesisedbytheMichiganCancerFoundationin1966underagrantfromtheNationalCancerInstitute.109ResearchersfromYaleUniversitythendiscovereditsantiretroviralactivityandappliedforapatent
inDecember1987,mostlyindevelopedcountries,fortheuseofd4Ttotreatpatientsinfectedwithretroviruses.110ThispatentshouldhaveexpiredinDecember2007,buttheprotectionwasextendeduntiltheendof2008intheU.S.anduntil2011inmostEuropeancountries.BMSmarketsd4TunderamarketinganddistributionlicencefromYaleUniversity.
•Patentshaveexpiredinmostothercountriesatthispoint.
PRICE INFORMATIONDeveloping country prices in US$ per patient per year, as quoted by companies. Thepriceinbracketscorrespondstothepriceofonecapsule/doseofpowderfororalsolution.ProductsincludedintheWHOListofPrequalifiedMedicinalProducts(asofApril2010)areinbold.
Dailydose
BMS
Aurobindo(CF) Cipla(CF) Hetero(CF) Matrix(CF) Ranbaxy(CF) StridesCategory1countries
Category2countries
Whocanaccessthisprice?
Seeannex2&annex7 Norestrictions
d4T1mg/mlpowderfororalsolution
20ml 51 (0.007/ml)
58 (0.008/ml)
58 (0.008/ml)
44 (0.006/ml)
d4T15mgcapsule
- (0.082) (0.093) (0.026) (0.024) (0.025)
d4T20mgcapsule
- (0.089) (0.093) (0.027) (0.025) (0.028)
d4T30mgcapsule
2 48 (0.066)
68 (0.093)
20 (0.028)
26(0.035)
21 (0.029)
24 (0.033)
26 (0.035)
22 (0.030)
(CF)TheClintonFoundationhasnegotiatedwiththismanufacturerforreducedpricesonsomeformulationsforcountriesintheirconsortium.Seeannex13fordetails.
Untangling the Web of ARV Price Reductions | Please check utw.msfaccess.org ��
ST
AV
UD
INE
( d�
T )
NU
CL
EO
SID
E &
NU
CL
EO
TID
E R
EV
ER
SE
TR
AN
SC
RIP
TA
SE
INH
IBIT
OR
S ( N
RT
I & N
tRT
I )
SPOTLIGHT ON ACCESS ISSUES
Formanyyears,thestavudine-containing(d4T)regimenhasplayedacrucialroleinARTscale-upinresource-limitedsettings,duetoitsavailabilityinafixed-dosecombinationand,mostimportantly,itslowcost.d4Tremainsawidely-usedARVinfirst-lineregimens.
InDecember2009,WHOreleasednewrecommendationsforantiretroviraltherapyforHIVinadultsandadolescents.Thesenewrecommendationsadvisecountriestophaseoutstavudine-basedregimensbecauseoftheirlong-termirreversiblesideeffectsandtomovetowardszidovudine(AZT)ortenofovir-based(TDF)first-lineregimens.9
PatentsYaleUniversitydidnotapplyforpatentsinmostdevelopingcountriesexceptforSouthAfrica.Therefore,genericmanufacturersfromcountrieswithmanufacturingcapacity,suchasBrazil,China,IndiaorThailandcouldlegallymanufactureandexportaffordablegenericversionsofd4T.
InSouthAfrica,whereBMSmarketedd4TunderanexclusivelicensefromYale,thedrugwas34timesmoreexpensivethangenericversionsavailableinothercountries.ThispromptedapatentcontroversyinMarch2001,particularlyasthemedicinehadbeendevelopedwithpublicfunds.Afterpressurefromresearchers,students,andaccessadvocates,YalerenegotiateditslicensewithBMStoallowtheimportationofmoreaffordablegenericversionsofd4TtoSouthAfrica.109
PaediatricsStavudineisapprovedforuseinchildren.
Thepaediatricformulationofd4Tisnotadaptedforresource-limitedsettingsasitissuppliedasapowderthatrequiresreconstitutionwithclean,safewater,andoncereconstituted,mustberefrigerated.
Genericmanufacturershavebeendevelopingbothdoubleandtriplefixed-dosecombinationsincludingd4T.Forpaediatricuse,twod4t-containingtripleFDCsareincludedinWHOListofPrequalifiedMedicinalProducts.
Dec03
May03
Feb05
Apr04
Jun06
Jun05
Jun 07
Jun 08
Dec09
US$
pp
y
Month/Year
60
50
40
30
20
10
0Jun10
lowest originator price
generic priced4T 30mg capsule
20
36
49 48
Evolution of the lowest price quoted for developing countries since �00�:
AsofApril2010,thereweresixgenericsourcesofd4T30mgcapsuleincludedintheWHOListofPrequalifiedMedicinalProducts.Theonewiththelowestpriceisshownhere.
Médecins Sans Frontières | July 2010
GENERAL INFORMATION
•Therapeuticclass:nucleotidereversetranscriptaseinhibitor(NtRTI).
•Indicatedforfirst-andsecond-lineforadults,adolescentsandchildren.8,137
•Originatorcompanyandproductbrandname:Gilead,Viread.
•FirstapprovalbyU.S.FoodandDrugAdministration(FDA):October2001.17
Evolution of the lowest price quoted for developing countries since �00�:
AsofApril2010,therewerefourgenericsourcesofTDF300mgtabletincludedintheWHOListofPrequalifiedMedicinalProducts.Theonewiththelowestpriceisshownhere.
Therehasbeena77%decreaseinthegenericpricesince2006,anda56%decreaseinthelowestoriginatorpricesince2003.
Dec03
May03
Feb05
Apr04
Jun06
Jun05
Jun 07
Jun 08
Dec09
Jun10
US$
pp
y
Month/Year
500
450
400
350
300
250
200
150
100
50
0
lowest originator price
generic priceTDF 300mg tablet
85
365
475
204
PRICE INFORMATIONDeveloping country prices in US$ per patient per year, as quoted by companies. Thepriceinbracketscorrespondstothepriceofonetablet.ProductsincludedintheWHOListofPrequalifiedMedicinalProducts(asofApril2010)areinbold.
•Includedinthe16theditionoftheWHOModelListofEssentialMedicines(EML).26
•Worldsalesoforiginatorproduct:2009:US$667million;2008:$621million;2007:$613million;2006:$689million;2005:$778million;2004:$783million.93,94,111,112,95,96
•ThebasicpatentontenofovirwasappliedforbytheAcademyofSciencesoftheformerCzechoslovakiain1986.Ithasnowexpiredinmostcountries.113
Gileadsubsequentlyappliedforadditionalpatentsrelatedtotenofovirdisoproxilin1997 114andtothefumaratesaltoftenofovirdisoproxilin1998.115Theseareduetoexpirein2017and2018,respectively.Inaddition,GileadandBMShaveappliedforpatentsonfixed-dosecombinationsofTDF/FTCandTDF/FTC/EFVwhich,ifgrantedindevelopingcountries,willnotexpirebefore2024and2026respectively.58,59
TENOFOVIR DISOPROxIL FUMARATE ( TDF )
TE
NO
FO
VIR
DIS
OP
RO
xIL
FU
MA
RA
TE
( T
DF )
NU
CLEO
SID
E &
NU
CLEO
TID
E R
EV
ER
SE T
RA
NSC
RIP
TA
SE I
NH
IBIT
OR
S (
NR
TI
& N
tRT
I )
��
Dailydose
Gilead
Aurobindo(CF) Cipla(CF) Hetero(CF) Matrix(CF) Ranbaxy StridesCategory1countries
Category2countries
Whocanaccessthisprice?
Seeannex2&annex9 Norestrictions
TDF300mgtablet 1 204 (0.559)
360 (0.986)
100 (0.275)
87 (0.237)
103(0.283)
85 (0.233)
152 (0.417)
146(0.400)
(CF)TheClintonFoundationhasnegotiatedwiththismanufacturerforreducedpricesonsomeformulationsforcountriesintheirconsortium.Seeannex13fordetails.
Untangling the Web of ARV Price Reductions | Please check utw.msfaccess.org
SPOTLIGHT ON ACCESS ISSUES
InDecember2009,WHOreleasednewrecommendationsforantiretroviraltherapyforHIVinadultsandadolescents.Thesenewrecommendationsadvisecountriestophaseoutstavudine-basedregimensbecauseoftheirlong-termirreversiblesideeffectsandtomovetowardszidovudineortenofovir-basedfirst-lineregimens.
Formanyyears,astavudine-based(d4T)regimenhasplayedacrucialroleinARTscale-upinresource-limitedsettings,duetoitsavailabilityinafixed-dosecombinationand,mostimportantly,itslowcost.d4Tremainsawidely-usedARVinfirst-lineregimens.
Itistime,however,forcountriestoinvestinamorerobust,TDF-containingfirst-lineregimen,suchasTDF/3TC/EFVorTDF/FTC/EFV,whichisonepill,onceaday.Whilethepricetodayisstillhigherthanad4T-basedregimen,thereisaneedtogenerategreaterdemandwhichwill,inturn,increasethecompetitionneededtofurtherdecreaseprices.9
Forsecond-linetreatment,TDFincombinationwithlamivudine(3TC)oremtricitabine(FTC)aretherecommendedNRTIbackbonestobeaddedtoaboostedproteaseinhibitor,ifstavudineorzidovudinehavebeenusedinthefirst-lineregimen.
TDFisalsoactiveagainsttheHepatitisBvirus(HBV)andthereforeplaysanimportantroleinco-infectedpatients.ForHIVpatientsrequiringtreatmentforHBV,thetreatmentshouldcontainTDFandeither3TCorFTC.
Gileadhasadifferentialpricingstructure(seeannex9)thathasbeenexpandedtoincludelower-middle-incomecountriesnotincludedinitsAccessProgram.
PatentsGileadhasappliedforpatentsrelatedtoTDFinmanydevelopingcountries,includingIndia,BrazilandChina.InBrazilandIndia,thesepatent
TE
NO
FO
VIR
DIS
OP
RO
xIL
FU
MA
RA
TE
( TD
F )
NU
CLEO
SID
E &
NU
CLEO
TID
E R
EV
ER
SE T
RA
NSC
RIP
TA
SE IN
HIB
ITO
RS ( N
RT
I & N
tRT
I )
��
applicationshavebeenopposedbycivilsocietygroups,aswellasbysomegenericmanufacturers.
Inamajorvictoryforaccesstomedicines,theIndianpatentofficerejectedseveralpatentapplicationsrelatingtoTDFinSeptember2009.Thepatentswererejectedonthegroundsthattheylackaninventivestep–theydonotmeettherequirementofenhancedefficacystipulatedunderSection3(d)ofIndia’spatentlaw.Further,combinationsofknownmoleculesarenotpatentableunderIndianpatentlaw.174,175,176
Nevertheless,divisionalapplications(atypeofpatentapplicationwhichcontainsmatterfromapreviouslyfiledapplication)havebeenfiledbyGileadforthisandotherpatentapplications.Thismeansthatalthoughthepatentwasnotgranted,thepatentapplicationsarestillpendingbeforethepatentoffice.116,117
ThesameistrueinBrazil,whereanestimated37,000PLHAareonTDF-basedtherapies.InApril2008,thegovernmentdeclaredtenofovirasamedicineofpublicinterestforpriorityexaminationpurposes.TheNationalInstituteonIndustrialProperty(INPI–Brazilianpatentoffice)publishedthepatentrejectionforTDFon30June2009.However,Gileadhasrequestedadivisionalpatent,whichhasbeenopposedbycivilsocietygroups.Inaddition,inJanuary2010,Gileadlaunchedalegalchallengeagainstthepatentoffice’sdecisiontorejectthepatent.
Followingoppositions(bymembersofIndianandBraziliancivilsociety)tothegrantofitspatentsinIndia,Gileadsignedlicensingagreementswith11genericmanufacturersinIndiaandoneinSouthAfrica,allowingthemtomanufactureandexportgenericversionsofTDFandTDF-basedFDCstoalimitedpre-definedlistofcountries,againstthepaymentofa5%royalty.103
Manufacturersthathavesignedtheseagreementsareunabletosupply
countriessuchasBrazilandChina,leavingthesecountriesunabletobenefitfromcompetitivepricesandimproveaccess.AfternegotiationwithGilead,BrazilistodaypayingUS$715perpatientperyearfortenofovir,overeighttimesthebestavailablegenericprice.129TheBraziliangovernmentiscurrentlysupportingthedevelopmentofgenericTDFthroughpartnershipsbetweenBrazilianpublicandprivatemanufactures.
AlthoughthelicensingagreementssignedbyGileadcancontributetoincreasedcompetitionandimprovedaccesstoaffordablemedicines,theyshouldalsobeofferedtomanufacturersoutsideIndia,andshouldnotincludegeographicmarketlimitations.
PaediatricsInMarch2010,TDFwasapprovedbytheU.S.FDAforuseinadolescentsolderthan12yearsoldandweighingmorethan35kg.118
Gilead’sPhaseIItrialinvolvingchildren(agedbetweentwoand12years),usinganoralpowderformulationisstillon-going.Suchdata,providedappropriateformulationsaredeveloped,willbecrucialtoaddresstheurgentneedsofthispaediatricpopulation.
InMarch2009,U.S.FDAgrantedTDFanOrphanDrugdesignationfortreatmentofpaediatricHIVinfections.119Gileadisnowentitledtosevenyearsofmarketingexclusivityforthedesignatedpaediatricindication,taxcreditsforclinicalresearchandcanapplyforgrantstodefraythecostofclinicaltrials.120
�� Médecins Sans Frontières | July 2010
ZIDOVUDINE ( AZT or ZDV )
GENERAL INFORMATION
•Therapeuticclass:nucleosidereversetranscriptaseinhibitor(NRTI).
•Indicatedforfirst-andsecond-lineforadults,adolescentsandchildren.8,137
•Originatorcompanyandproductbrandname:GlaxoSmithKline(GSK),Retrovir.InApril2009,PfizerandGSKjointlyannouncedthecreationofViiV,anewjointventurefocusingsolelyontheR&DandcommercialisationofHIVmedicines.
•FirstapprovalbyU.S.FoodandDrugAdministration(FDA):March1987.17
•Includedinthe16theditionoftheWHOModelListofEssentialMedicines(EML).26
•Worldsalesoforiginatorproduct:2005:US$84million;2004:$80million.After2005,therearenosalesfiguresforthisproductlistedinthecompany’sannualreport.78,79
•AZTwasfirstdiscoveredin1964asananti-cancermedicine.TheU.S.NationalInstitutesofHealthdidthemajorityoftheresearchthatshowedthedrug’seffectivenessasanantiretroviral.GlaxoWellcomefiledforpatentsonAZTforthetreatmentofAIDSandbroughtthedrugontothemarketin1987asoneofthemostexpensiveeversold.Patentshaveexpiredinmostcountriesatthispoint.
PRICE INFORMATIONDeveloping country prices in US$ per patient per year, as quoted by companies. Thepriceinbracketscorrespondstothepriceofonetablet/capsule/doseofsuspension.ProductsincludedintheWHOListofPrequalifiedMedicinalProducts(asofApril2010)areinbold.
ZID
OV
UD
INE
( A
ZT
or
ZD
V )
NU
CL
EO
SID
E &
NU
CL
EO
TID
E R
EV
ER
SE
TR
AN
SC
RIP
TA
SE
IN
HIB
ITO
RS (
NR
TI
& N
tRT
I )
Dailydose
ViiV Aurobindo(CF) Cipla(CF) Hetero(CF) Matrix(CF) Ranbaxy(CF)
Whocanaccessthisprice? Seeannex2 Norestrictions
AZT10mg/mlsuspension 20ml 234 (0.032/ml)
66 (0.009/ml)
80 (0.011/ml)
66(0.009/ml)
AZT60mgtablet 4 115 (0.079)
AZT100mgcapsule - (0.122) (0.051) (0.050)
AZT250mgcapsule - (0.276)
AZT300mgtablet 2 161 (0.221)
101 (0.138)
97 (0.133)
100 (0.137)
91 (0.125)
91 (0.125)
(CF)TheClintonFoundationhasnegotiatedwiththismanufacturerforreducedpricesonsomeformulationsforcountriesintheirconsortium.Seeannex13fordetails.
Untangling the Web of ARV Price Reductions | Please check utw.msfaccess.org ��
SPOTLIGHT ON ACCESS ISSUES
Formanyyears,thestavudine-containing(d4T)regimenhasplayedacrucialroleinARTscale-upinresource-limitedsettings,duetoitsavailabilityinafixed-dosecombinationand,mostimportantly,itslowcost.d4Tremainsawidely-usedARVinfirst-lineregimens.
InDecember2009,WHOreleasednewrecommendationsforantiretroviraltherapyforHIVinadultsandadolescents.Thesenewrecommendationsadvisecountriestophaseoutstavudine-basedregimensbecauseoftheirlong-term
irreversiblesideeffectsandtomovetowardszidovudine(AZT)ortenofovir-based(TDF)first-lineregimens.9
Forsecond-linetreatment,andiftenofovirhasbeenusedinthefirst-line,AZTincombinationwithlamivudine(3TC)istherecommendedNRTIbackbone,towhichaboostedproteaseinhibitor(PI)shouldbeadded.
Patents
Patentshaveexpiredinmostcountriesatthispoint.
Paediatrics
AZTisapprovedforuseandiswidelyusedinchildren.
Genericmanufacturershavebeendevelopingbothdoubleandtriplepaediatricfixed-dosecombinationsincludingAZT.Today,however,therearefourpaediatricFDCs
containingAZTthatareincluded
inWHOListofPrequalified
MedicinalProducts.
Todaythereisonegenericversion
ofAZT60mgwhichisprequalified
byWHO.
Oct 01
Dec 02
Jun02
Dec03
May03
Feb05
Apr04
Jun06
Jun05
Jun 07
Jun 08
Dec09
Jun10
US$
pp
y
Month/Year
800
700
600
500
400
300
200
100
0
lowest originator price
generic priceAZT 300mg tablet
684
161
91
193
Evolution of the lowest price quoted for developing countries since �00�:
AsofApril2010,thereweresevengenericsourcesofAZT300mgtabletincludedintheWHOListofPrequalifiedMedicinalProducts.Theonewiththelowestpriceisshownhere.
Since2001,theoriginatorpricehasdecreasedby76%,whilethegenericpricehasdecreasedby53%.
ZID
OV
UD
INE
( AZT
or Z
DV
)N
UC
LE
OSID
E &
NU
CL
EO
TID
E R
EV
ER
SE
TR
AN
SC
RIP
TA
SE
INH
IBIT
OR
S ( N
RT
I & N
tRT
I )
�0 Médecins Sans Frontières | July 2010
GENERAL INFORMATION
•Therapeuticclass:proteaseinhibitor(PI).
•BoostedATVisindicatedforsecond-lineforadultsandadolescents.8
•Originatorcompanyandproductbrandname:Bristol-MyersSquibb(BMS),Reyataz.
•FirstapprovalbyU.S.FoodandDrugAdministration(FDA):June2003.17
ATAZANAVIR ( ATV )
•Includedinthe16theditionof
theWHOModelListofEssential
Medicines(EML).26
•Worldsalesoforiginatorproduct:2009:
US$1.4billion;2008:$1.3billion;
2007:$1.1billion;2006:$931million;
2005:$696million;2004:$369million;
2003:$81million.121,50,122,108,123
•ThebasicpatentwasfiledinApril1997byNovartisandisexpectedtoexpireinApril2017.124Bristol-MyersSquibbismanufacturingATVunderlicencefromNovartis.BMSalsoappliedforpatentsonthecrystallinebisulfatesaltofATVinDecember1998125andonaprocessforpreparingthebisulfatesaltandnovelformsin2005.126
PRICE INFORMATIONDeveloping country prices in US$ per patient per year, as quoted by companies. Thepriceinbracketscorrespondstothepriceofonecapsule.ProductsincludedintheWHOListofPrequalifiedMedicinalProducts(asofApril2010)areinbold.
Dailydose
BMS
Matrix(CF)Category1countries
Category2countries
Whocanaccessthisprice? Seeannex2&annex7 Norestrictions
ATV150mgcapsule 2* 353 (0.484)
431 (0.590)
ATV200mgcapsule - (0.602) (0.743)
ATV300mgcapsule 1*256(0.700)
AT
AZ
AN
AV
IR (
AT
V )
PR
OT
EA
SE
IN
HIB
ITO
RS (
PI )
*ThedoseofATVmustbeboostedwithRTV100mgonceaday.
(CF)TheClintonFoundationhasnegotiatedwiththismanufacturerforreducedpricesonsomeformulationsforcountriesintheirconsortium.Seeannex13fordetails.
Untangling the Web of ARV Price Reductions | Please check utw.msfaccess.org ��
AT
AZ
AN
AV
IR ( A
TV
)P
RO
TE
ASE
INH
IBIT
OR
S ( P
I )
SPOTLIGHT ON ACCESS ISSUES
InDecember2009,WHOrecommendationsforsecond-linetherapyincludedtwo‘preferred’proteaseinhibitors(PI),tobetakenincombinationwithtwoNRTIs.Theyareatazanavir(ATV)boostedwithritonavir(RTV)andlopinavir/ritonavir(LPV/r).9Withitsonce-a-daydosingATVisthemostpatient-friendlyPIofthetwo.
ATV,likeallPIs(withtheexceptionofnelfinavir(NFV),requiresboostingwithRTV.Abbott’sheat-stableritonavirreceivedmarketingapprovalintheU.S.andEuropeinearly2010.RegisteringthisnewformulationindevelopingcountrieswillbecrucialinordertoallowtheuseofotherPIsthanlopinavir.
TherequiredadditionofRTVasaboostermustalsobeconsideredinthefinalcostofusingATV.
AsATVisoneofthetwoPIsrecommendedbyWHO,thereisanurgentneedforgenericmanufacturerstosupplyaheat-stableATV/rfixed-dosecombination.Currentlythisfixed-dosecombinationisnotproducedbytheoriginatorcompanies.
PatentsPatentapplicationsrelatedtoATVhavebeenfiledbyNovartisandBMSinmostdevelopingcountrieswithgenericpharmaceuticalproductioncapacity,includingBrazil,China
andIndia.MostpatentshavebeengrantedinBrazilandChina.InIndia,wherethepatentapplicationsarestillunderexamination,civilsocietyorganisationsfiledapre-grantoppositiontoNovartis’sbasicpatentapplicationonthegroundsoflackofnovelty,127buttheotherpatentapplicationswarrantadditionalpre-grantoppositions.
Inaddition,AbbotthasfiledpatentapplicationsonRTVinIndiaandotherdevelopingcountries,which,ifgranted,willblockthedevelopmentofandaccesstogenericATV/rfixed-dosecombinations.
BMSinFebruary2006grantedtechnologytransferandvoluntarylicencestotwogenericmanufacturers(EmcureandAspen)tomanufactureandsellATV.InFebruary2008,EmcurereceivedU.S.FDAtentativeapprovalforthe100mg,150mgand200mgATVcapsules.Underthetermsofthelicenses,however,salesoftheseproductsareroyalty-freebutarerestrictedtosub-SaharanAfrica.
BMShasaseparateagreementwithEmcurethatcoversIndia.128
LicensingagreementsinIndiashouldnotbenecessaryifpatentoppositionsaresuccessful.Ifpatentsaregranted,Indiaandothercountriescouldissuecompulsorylicencestoenableunrestrictedcompetitionfrom
genericmanufacturers,inordertobringpricesdown,increaseaccessandfacilitatethedevelopmentofanATV/rfixed-dosecombination.
BMS’sdifferentialpricingstructureislimitedtosub-SaharanAfricaandlow-incomecountries.Thisstructureleavesmiddle-incomecountriessuchasBrazilpayingmorethanUS$1,400perpatientperyear,whichisprohibitiveformanyofthesecountries.129
Paediatrics
InMarch2008,ATVwasapprovedforuseinchildrenbetween6and18yearsofage.17
In2008,WHOrecommendedearlytreatmentforallHIV-positivechildren,andchildrenwhohavebeenexposedtonevirapineeitherthroughtheirmotherorthroughasingledoseinapreventionofmother-to-childtransmission(PMTCT)programme.WHOrecommendsthesechildrenshouldbestartedonaPI-basedregimen.130Today,theonlyoptionforthesechildrenistheLPV/rformulation.
Tosimplifytreatmentforallchildren,thereisanurgentneedforstudiesonATVtobecompleteddowntoinfants,andchild-adaptedformulationstobemadeavailable.
�� Médecins Sans Frontières | July 2010
GENERAL INFORMATION
•Therapeuticclass:proteaseinhibitor(PI).
•BoostedDVRislistedinWHOguidelineasapotentialthird-linedrug.8
•Indicatedfortreatment-experiencedpatients,suchasthosewithHIV-1strainsresistanttomorethanoneproteaseinhibitor(adults).Itisalsoindicatedindevelopedcountriesfortreatment-naivepatients.131
DARUNAVIR ( DRV )
•Originatorcompanyandproductbrandname:Tibotec(adivisionofJohnson&Johnson),Prezista.
•FirstapprovedbytheU.S.FoodandDrugAdministration(FDA):June2006.17
•Worldsalesoforiginatorproduct:therearenosalesfigureslistedinthecompany’sannualreport.
•Notincludedinthe16theditionoftheWHOModelListofEssentialMedicines(EML).26
•ThebasicpatentwasappliedforbySearleandMonsantoinAugust1993,132andisduetoexpirein2013.Subsequently,NIHandtheUniversityofIllinoisappliedforpatentsmorespecificallyrelatedtodarunavirin1999133andlicensedthemtoTibotecfordevelopment.134Tiboteclaterappliedforpatentsrelatedtoimprovedformsandcombinationsofdarunavir.
PRICE INFORMATIONDeveloping country prices in US$ per patient per year, as quoted by companies. Thepriceinbracketscorrespondstothepriceofonetablet.
DA
RU
NA
VIR
( D
RV
)P
RO
TE
ASE
IN
HIB
ITO
RS (
PI )
Dailydose Tibotec
Whocanaccessthisprice? Seeannex2
DRV300mgtablet 4*1095(0.750)
*ThedoseofDRVmustbeboostedwithRTV100mgtwiceaday.
Untangling the Web of ARV Price Reductions | Please check utw.msfaccess.org ��
SPOTLIGHT ON ACCESS ISSUES
InDecember2009,WHOreleasednewrecommendationswhichforthefirsttimecallfortheneedofthird-linetherapy.Asmanystudiesareongoing,drugslikelytohaveanti-HIVactivityinthird-lineregimensareboosteddarunavir,etravirineandraltegravir.9
Tibotecsignedaroyalty-free,non-exclusivelicenseagreementwithAspenofSouthAfricaon4April2007.ThisgrantsAspentherighttoregister,packageanddistributedarunavir(DRV)insub-SaharanAfrica.InDecember2008,Tibotecannouncedthesigningofaroyalty-free,non-exclusivelicenseagreementwithEmcuretodistributeDRVinIndia.136Theseagreementsexcludeotherlow-andmiddle-incomecountries,forwhichthepricepaidinwealthycountries,atoverUS$11,400perpatientperyear,isprohibitive.37
Morerecently,Tiboteccompletedasupplyandco-marketingagreementwithAspenPharmacarecoveringallofAfrica.Underthisagreement,Aspenwillhandleregulatory,registration,anddistributionactivities.Atthetimeofwriting,theAspen/Tibotecproductisregisteredinatleasteightcountrieswithapplicationsinprocessin11others,primarilyforthe400mgproductbutalsofor300mgandpaediatricformulations.PatientnumbersinAfricaforDRVarestillsmall,andAspenhasagreedtoa$1,095perpatientperyearfor300mgand400mgformulations.
InBrazil,DRVwasincludedinthegovernment’sguidelinesin2008,
butat$6,037perpatientperyear(boostedwithritonavir),itisveryexpensive.129
DRV,likeallPIs(withtheexceptionofnelfinavir(NFV)),requiresboostingwithritonavir(RTV).Abbott’sheat-stableritonavirreceivedmarketingapprovalintheU.S.andEuropeinearly2010.RegisteringthisnewformulationindevelopingcountrieswillbecrucialinordertoallowtheuseofotherPIsthanlopinavir.
TherequiredadditionofRTVasaboostermustalsobeconsideredinthefinalcostofusingDRV.
Thereisaneedforgenericmanufacturerstosupplyaheat-stableDRV/rfixed-dosecombination.Currentlythisfixed-dosecombinationisnotproducedbytheoriginatorcompanies.
PatentsEventhoughbasicpatentsrelatedtoDRVcouldnotbeappliedforinIndiabefore1995,TibotechasappliedforseveralpatentsinIndiarelatedtonewformsandcombinationsofDRVwithtenofovir(TDF)andritonavir(RTV),someofwhichhavebeenopposedbygenericmanufacturers.MostofthesepatentapplicationsremainunderreviewattheIndianpatentoffice.TheIndianpatentofficerecentlyrejectedtheDRVpatentrelatedtopseudopolymorph(whichwouldhavebeenduetoexpirein2023).AvoluntarylicensefortheDRVpseudopolymorphhasbeengrantedinSouthAfrica.
InChina,patentsrelatedtoracemicandpseudopolymorphicformsofDRV,methodsforpreparing
intermediatecompoundsofDRVanduseofDRVincombinationwithotherARVs,havebeengrantedtoTibotec.39
Similarly,manypatentshavebeenfiledinBrazil,suchasthoserelatedtothecombinationofDRVwithTDFandRTV,aswellasthoserelatedtothepreparationofkeyintermediatesandthepseudopolymorphicform.
PaediatricsInDecember2008,DRVwasapprovedforuseinchildrenbetweensixand18yearsofage.17
Apaediatric75mgtabletisavailable,butTibotechasnotprovidedpriceinformationforthisproduct.Itishowever,availableonacompassionateusebasis(freeofcharge)forsub-SaharanAfricaandleast-developedcountries,untilapre-approvalaccessprogrammeisestablishedwithalocalpartner.
ThePaediatricAntiretroviralWorkingGroupofWHOconsidersthedevelopmentofafixed-dosecombinationcontainingdarunavirandritonavirtobeahighpriority,thoughitisstillunclearwhattheratiooftheco-formulationwillbe.137
DA
RU
NA
VIR
( DR
V )
PR
OT
EA
SE
INH
IBIT
OR
S ( P
I )
Médecins Sans Frontières | July 2010
PR
OT
EA
SE
IN
HIB
ITO
RS (
PI )
FO
SA
MP
RE
NA
VIR
( F
PV
or
f-A
PV
)
GENERAL INFORMATION
•Therapeuticclass:proteaseinhibitor(PI).
•NotcurrentlyincludedinWHOguidelines.
•Originatorcompanyandproductbrandname:GlaxoSmithKline(GSK)andVertexPharmaceuticals,Lexiva.InApril2009,PfizerandGSKjointlyannouncedthecreationofViiV,anewjointventurefocusingsolelyontheR&DandcommercialisationofHIVmedicines.
FOSAMPRENAVIR ( FPV or f-APV )
SPOTLIGHT ON ACCESS ISSUES
InDecember2009,WHOrecommendationsforsecond-linetherapyincludedtwo‘preferred’proteaseinhibitors(PI),tobetakenincombinationwithtwoNRTIs.Theyareatazanavir(ATV)boostedwithritonavir(RTV)andlopinavir/ritonavir(LPV/r).9Asfosemprenavir(FPV)wasnotidentifiedasoneofthepriorityproducts,itsusewillbelimitedinthedevelopingworld.9
WhileFPV/rbasedregimensshowgoodantiviralefficacyandaregenerallywelltoleratedintherapy-naïvepatients,theexperienceofthisdrugindevelopedcountriesislimitedandlittlecomparativedataisavailableintreatment-experiencedpatients.141
FPV,likeallPIs(withtheexceptionofnelfinavir(NFV)),requiresboostingwithritonavir(RTV).
Abbott’sheat-stableritonavirreceivedmarketingapprovalintheU.S.andEuropeinearly2010.RegisteringthisnewformulationindevelopingcountrieswillbecrucialinordertoallowtheuseofotherPIsthanlopinavir.
TherequiredadditionofRTVasaboostermustalsobeconsideredinthefinalcostofusingFPV.
Patents
Patentapplicationshavebeenfiledforinmanydevelopingcountries.InBrazilthebasicpatentwasrejectedbythepatentoffice,althoughinDecember2009thecompanyfiledanappealagainstthedecision.
InChina,SouthAfrica,ARIPOandOAPIcountries,142mostpatentshavebeengranted.
InIndia,patentapplicationsontheFPVsalts,includingcalcium,havebeenfiledandarependingreviewbythepatentoffice.
Therearenogenericformulationsofthisproductavailabletoday.
Paediatrics
FPVwasapprovedforuseinchildrenabovetheageoftwoinOctober200717andapaediatricsuspensionisavailable.
•FirstapprovedbytheU.S.FoodandDrugAdministration(FDA)on:October2003.17
•Notincludedinthe16theditionoftheWHOModelListofEssentialMedicines(EML).26
•Worldsalesoforiginatorproduct:therearenosalesfigureslistedinthecompany’sannualreport.
•ThebasicpatentwasappliedforbyVertexPharmaceuticalsinMarch1998,138andduetoexpirein2018.Fosamprenavir,aphosphateesterprodrugofamprenavir,139wasdevelopedandlaunchedbyGSK,underlicensefromVertex.GSKalsoholdspatentsrelatedtoacrystallineformofthecalciumsaltofFPV,140duetoexpirein2019.
��
PRICE INFORMATION
Dailydose ViiV
Whocanaccessthisprice? Seeannex2
FPV50mg/mlsuspension 12ml*648(0.148/ml)
FPV700mgtablet 2*1222(1.674)
*ThedoseofFPVmustbeboostedwithRTV100mgtwiceadayforadults.
Developing country prices in US$ per patient per year, as quoted by companies. Thepriceinbracketscorrespondstothepriceofonetablet/doseoforalsuspension.
Untangling the Web of ARV Price Reductions | Please check utw.msfaccess.org
IND
INA
VIR
( IDV
)P
RO
TE
ASE
INH
IBIT
OR
S ( P
I )
��
INDINAVIR ( IDV )
GENERAL INFORMATION
•Therapeuticclass:proteaseinhibitor(PI).
•NotcurrentlyincludedinWHOguidelines.
•Originatorcompanyandproductbrandname:Merck,Crixivan.
•FirstapprovalbyU.S.FoodandDrug
Administration(FDA):March1996.17
•Includedinthe16theditionof
theWHOModelListofEssential
Medicines(EML).26
•Worldsalesoforiginatorproduct:therearenosalesfigureslistedinthecompany’sannualreport.
•ThebasicpatentwasfiledforbyMerckin1991andisduetoexpirein2012incountriesgranting20-yearpatents.143
PRICE INFORMATIONDeveloping country prices in US$ per patient per year, as quoted by companies. Thepriceinbracketscorrespondstothepriceofonecapsule.ProductsincludedintheWHOListofPrequalifiedMedicinalProducts(asofApril2010)areinbold.
Dailydose
Merck
Aurobindo Cipla HeteroCategory1countries
Category2countries
Whocanaccessthisprice? Seeannex2&annex10 Norestrictions
IDV400mgcapsule 4* 394 (0.270)
686 (0.470)
292(0.200)
422(0.289)
390 (0.267)
Evolution of the lowest price quoted for developing countries since �00�:
AsofApril2010,thereweretwogenericsourcesofIDV400mgcapsuleincludedintheWHOListofPrequalifiedMedicinalProducts.Theonewiththelowestpriceisshownhere.
SPOTLIGHT ON ACCESS ISSUES
InDecember2009,WHOrecommendationsforsecond-linetherapyincludedtwo‘preferred’proteaseinhibitors(PI),tobetakenincombinationwithtwoNRTIs.Theyareatazanavir(ATV)boostedwithritonavir(RTV)andlopinavir/ritonavir(LPV/r).AsIDVwasnotidentifiedasoneofthepriorityproducts,itsusewillbelimitedinthedevelopingworld.9
Themainconcernwasthatatastandarddoseof800mgwith100mgritonavir(RTV)twiceaday,IDVislesswelltoleratedthanotherPIs,particularlyinhotclimates.141Therehavebeensomesmallstudiesto
supportalowerdoseofIDV+RTV400+100mgtwiceadaywiththeaimtoreducetoxicity.TheU.S.FDAhasalsoapprovedtheuseofIDVat800mgeveryeighthourswithoutRTV.
IDV,likeallPIs(withtheexceptionofnelfinavir(NFV)),requiresboostingwithRTV.Abbott’sheat-stableritonavirreceivedmarketingapprovalintheU.S.andEuropeinearly2010.RegisteringthisnewformulationindevelopingcountrieswillbecrucialinordertoallowtheuseofotherPIsthanlopinavir.
TherequiredadditionofRTVasaboostermustalsobeconsideredinthefinalcostofusingIDV.
SomegenericmanufacturershavestoppedproductionofIDV,oronlymanufactureitforspecificorders,becauseofadecreaseindemandforthisproduct.
PatentsInBrazil,indinavirisoneoftheARVsproducedlocally.Thepatentapplicationwasfiledin1994,atatimewhenthecountrydidnotgrantpatentsonpharmaceuticals.Forthisreason,itwasrejected.
PaediatricsTheoptimaldosingregimenfortheuseofIDVinpaediatricpatientshasnotbeenestablishedandnopaediatricformulationexists.144
Oct 01
Dec 02
Jun02
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Feb05
Apr04
Jun06
Jun05
Jun 07
Jun 08
Dec09
Jun10
US$
pp
y
Month/Year
1000
800
600
400
200
0
lowest originator price
generic priceIDV 400mg capsule
390394
876
600
*ThedoseofIDVmustbeboostedwithRTV100mgtwiceaday.
Médecins Sans Frontières | July 2010
LO
PIN
AV
IR/R
ITO
NA
VIR
( L
PV
/r
)P
RO
TE
ASE
IN
HIB
ITO
RS (
PI )
LOPINAVIR/ RITONAVIR ( LPV/r )
��
GENERAL INFORMATION
•Therapeuticclass:boostedProtease
Inhibitor(PI)inadoublefixed-dose
combination.
•Indicatedforsecond-line,foradults,
adolescentsandchildren.8,137
•FirstapprovalbyU.S.FoodandDrug
Administration(FDA):September2000
(soft-gelcapsules);October2005
(heat-stabletablets).17
Evolution of the lowest quoted price for developing countries since �00�:
AsofApril2010,therewasnogenericsourceofLPV/r133/33mgsoft-gelcapsuleincludedintheWHOListofPrequalifiedMedicinalProducts,sothelowestpricedgenericisconsideredinthisgraph.TherewerehowevertwogenericsourcesofLPV/r200/50mgheat-stabletabletincludedinthelist.Theonewiththelowestpriceisshownhere.
ThegenericpriceofLPV/r200/50mgheat-stabletablethasdecreasedby54%since2007.
Dec 02
Jun02
Dec03
May03
Feb05
Apr04
Jun06
Jun05
Jun 07
Jun 08
Dec09
Jun10
US$
pp
y
Month/Year
lowest originator price (200/50mg heat-stable)
generic price (133/33mg soft-gel)
4000
1000
800
600
400
200
lowest originator price (133/33mg soft-gel)
generic price (200/50mg heat-stable)
1034
LPV/r
3833
500 500
609
440
500
475
•Originatorcompanyandproductbrandname:AbbottLaboratories,Kaletra/Aluvia.
•Includedinthe16theditionoftheWHOModelListofEssentialMedicines(EML).26
•Worldsalesoforiginatorproduct:2009:US$1.366billion;2008:$1.47billion;2007:$1.32billion;2004:$897million;2003:$754million;2002:$551million;2001:$292million.145,146,147
•Mostpatentsrelatedtoritonavir(RTV)alsocoverLPV/r.ThebasicpatentrelatedtoLPVwasappliedforbyAbbottin1996.148
•Inaddition,AbbottappliedforpatentsmorespecificallyrelatedtoLPV/rsoft-gelcapsulesin1997149whichareduetoexpirein2017.Anapplicationforapatentontheheat-stabletabletformulationwasalsofiledin2004,150which,ifgranted,wouldrununtil2024.
PRICE INFORMATIONDeveloping country prices in US$ per patient per year, as quoted by companies. Thepriceinbracketscorrespondstothepriceofonecapsule/tablet/doseoforalsolution.ProductsincludedintheWHOListofPrequalifiedMedicinalProducts(asofApril2010)areinbold.
Dailydose
Abbott
Aurobindo(CF) Cipla(CF) Hetero(CF) Matrix(CF)Category1countries
Category2countries
Whocanaccessthisprice? Seeannex2&annex8 Norestrictions
LPV/r80/20mg/mloralsolution 4ml 176 (0.121/ml)
400 (0.274/ml)
LPV/r100/25mgheat-stabletablet 3 165 (0.151)
376 (0.343)
219 (0.200)
228 (0.208)
LPV/r133/33mgsoft-gelcapsule 6 500 (0.228)
1000 (0.457)
609(0.278)
LPV/r200/50mgheat-stabletablet 4 440 (0.301)
1000 (0.685)
475 (0.325)
463(0.317)
493(0.338)
486 (0.333)
(CF)TheClintonFoundationhasnegotiatedwiththismanufacturerforreducedpricesonsomeformulationsforcountriesintheirconsortium.Seeannex13fordetails.
Untangling the Web of ARV Price Reductions | Please check utw.msfaccess.org
LO
PIN
AV
IR/R
ITO
NA
VIR
( LP
V/r )
PR
OT
EA
SE
INH
IBIT
OR
S ( P
I )
SPOTLIGHT ON ACCESS ISSUES
InDecember2009,WHOrecommendationsforsecond-linetherapyincludedtwo‘preferred’proteaseinhibitors(PI),tobetakenincombinationwithtwoNRTIs.Theyareatazanavir(ATV)boostedwithritonavir(RTV)andlopinavir/ritonavir(LPV/r).9
Theheat-stableformulationofLPV/rmanufacturedbyAbbottandIndiangenericcompaniesisnowmarketedindevelopingcountries.Incomparisontotheolder,soft-gelcapsuleformulation,thenewformulationhasalowerpillcount(reducingtheburdenfromsixtofourpillsperday),thereisnoneedforrefrigeration,andtherearenodietaryrestrictions.Itisnowapprovedasonce-a-daydosingintreatment-experiencedpatientswithfewerthanthreelopinavirresistance-associatedmutations.17Thisshouldenhanceadherence.However,pillburdenremainsanissue.
Theentryofgenericmanufacturersishavingapositiveeffectonthemarket,andpricesaredeclining.TheClintonFoundation’smostrecentannouncementhassomegenericmanufacturersofferingpricesofUS$440perpatiantperyear(seeannex13fordetails).
PatentsInIndia,Abbotthasappliedforseveralpatentsonthesoliddosageformulationandpolymorphicformsoflopinavir(LPV),ritonavir(RTV)andontheheat-stablecombinationofLPV/r,anumberofwhichhavebeenopposedbycivilsocietyorganisations151andgenericcompanies.Followingapre-grantoppositiontotheapplicationrelatedtothesoft-gelformulationofLPV/r,theapplicationwaswithdrawnbythecompany.OtheroppositionsarependingdecisionsbytheIndianpatentoffice.
Ifoneofthesepatentapplicationsisgranted,currentgenericcompetition,whichisbringingpricessubstantiallydownasdemandincreases,willbeunderthreat.
Indiaandothercountriescouldissuecompulsorylicencestoenableunrestrictedcompetitionfromgenericmanufacturerstocontinue.
InThailand,whereAbbottholdspatents,thepriceofLPV/rwasUS$2,200ppyin2007.InJanuary2007,theMinistryofPublicHealthissuedacompulsorylicencetoimportmoreaffordablegenericversionsofthedrugfromIndia.53ThailandfacedfiercecriticismfromdevelopedcountriesandmultinationalpharmaceuticalcompaniesandAbbott’sresponsewastowithdrawallregistrationapplicationsinThailandforitsnewproducts,includingtheheat-stableLPV/r.ThailandtodayimportsgenericLPV/rfromIndiafor$793ppy.54
InresponsetoThailand’scompulsorylicence,Abbottreducedthepricefor40middle-incomecountriesforboththesoft-gelandtheheat-stableversionto$1,000ppy,includingBrazilwhichatthetimewaspaying$1,380.152
Indeed,thebasicpatentforLPV/risprotectedinBrazilundertheso-called‘pipelinemechanism’,aprovisioninBrazilianpatentlawdeemedtobeinexcessoftheminimumstandardsforintellectualpropertyprotectionundertheTRIPSAgreement.
In2007,theNationalFederationofPharmacists(Fenafar)–onbehalfoftheBrazilianNetworkfortheIntegrationofPeoples(Rebrip)-requestedtheBrazilianProsecutorGeneralconsideroverturningthepipelinemechanismasunconstitutional.TheyarguethatthesepatentsshouldnotbegrantedinBrazilonthebasisthattheyhadnotgonethroughtheregularanalysisprocessforpatentapplicationsandthattheygoagainstthepublicinterest.In2009,theProsecutorGenerallodgedacaseforunconstitutionalitywiththeSupremeCourt.MSF-Brazilisactivelyfollowingthecase.153
Paediatrics LPV/risapprovedforuseinchildrenfromtwoweeksold.17
Inearly2007,AbbottreleasedapaediatricLPV/r100/25mgheat-stabletablet.Whilethisnewformulationiswelcome,itdoesnothelptheyoungestpatients,asthetabletis15mmlongandcannotbecrushed,leavingthisformulationunsuitableforchildrenwhocannotswallowtablets.
Thealternativeforthesesmallchildrenisasolutionthatrequiresrefrigerationuntildispensing,afterwhichitmustbestoredbelow25°Cfornomorethansixweeks.Furthermore,thesolutionconsistsof42%alcoholandhasaveryunpleasanttaste.
Thereisanurgentneedformoreadaptedheat-stablepaediatricformulationofLPV/r(suchassolublegranulesorsprinkles)foryoungchildrenwhocannotswallowtheexistingtablet.Aheat-stablesprinkleinapaediatricdoseisunderdevelopmentbygenericcompanies.ThePaediatricAntiretroviralWorkingGroupofWHOconsidersthedevelopmentofaLPV/r40/10mgheat-stablesprinkletobeahighpriority.137
Todaytherearetwogenericsourcesofheat-stableLPV/r100/25mgincludedintheWHOListofPrequalifiedMedicinalProducts.
RecentchangesintheWHOguidelinesrecommendingthatallHIV-positivechildrenunderoneyearofagestartARVtherapyassoonaspossibleregardlessofclinicalstatus,combinedwiththerecommendationtostartallchildrenexposedtonevirapineonaPI-basedregimen,shouldresultinanincreaseddemandforthiscombinationforveryyoungchildren.130
��
�� Médecins Sans Frontières | July 2010
GENERAL INFORMATION
•Therapeuticclass:proteaseinhibitor(PI).
•NotcurrentlyincludedinWHOguidelines.
•Originatorcompanyandproductbrandname:Roche,Viracept.
•FirstapprovalbyU.S.FoodandDrugAdministration(FDA):March1997.17
NELFINAVIR ( NFV )
•Deletedfromthe16theditionoftheWHOModelListofEssentialMedicines(EML).26
•Worldsalesoforiginatorproduct:2004:US$259million.After2004,therearenosalesfigureslistedinthecompany’sannualreport.154
•Thebasicpatentwasappliedforin1994byAgouronPharmaceuticalsInc.,155andisduetoexpirein2014.AgouronPharmaceuticalsisnowasubsidiaryofPfizer.NFVwasdevelopedbyAgouronaspartofajointventurewithJapanTobacco,Inc.NFVissuppliedbyRocheoutsidetheU.S.,CanadaandJapan.156
PRICE INFORMATIONDeveloping country prices in US$ per patient per year, as quoted by companies. Thepriceinbracketscorrespondstothepriceofonetablet/gram.ProductsincludedintheWHOListofPrequalifiedMedicinalProducts(asofApril2010)areinbold.
Evolution of the lowest price quoted for developing countries since �00�:
AsofApril2010,therewasnogenericsourceofNFV250mgtabletincludedintheWHOListofPrequalifiedMedicinalProducts.Thelowestavailablegenericpriceisthereforeshownhere.
RochequotespricesinSwissFrancs(CHF),whichwereconvertedtoUS$onthedatereceived.FluctuationsintheUS$/CHFratewillthushaveanimpactonpricesusedinthegraph.
Oct 01
Dec 02
Jun02
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US$
pp
y
Month/Year
3500
3000
2500
2000
1500
1000
500
0
lowest originator price
generic priceNFV 250mg tablet
945
1566
3139
2924
Dailydose
Roche
CiplaCategory1countries
Category2countries
Whocanaccessthisprice? Seeannex2 Norestrictions
NFV50mg/goralpowder 24g 2129 (0.243/g)
2462 (0.281/g)
NFV250mgtablet 10 1566 (0.429)
2427 (0.665)
945(0.259)
NE
LF
INA
VIR
( N
FV
)P
RO
TE
ASE
IN
HIB
ITO
RS (
PI )
Untangling the Web of ARV Price Reductions | Please check utw.msfaccess.org ��
NE
LF
INA
VIR
( NF
V )
PR
OT
EA
SE
INH
IBIT
OR
S ( P
I )
SPOTLIGHT ON ACCESS ISSUES
Nelfinavir(NFV)istheonlyproteaseinhibitor(PI)thatdoesnotrequireboostingwithritonavir(RTV).
Thelargepillburden(10tabletsadayforanadult)anditshighpricemakeitaless-desirableoptionwhenselectingaPI.
InJune2007,RocherecalledallbatchesofNFVduetohighlevelsofEthylMethaneSulphonate(EMS),aby-productofthemanufacturingprocessandaknowncarcinogeninanimals.Roche’smarketinglicenceforNFVwassuspendedinEuropeandtheWHOprequalificationprojecttemporarilysuspendedtheproduct.InSeptember2007,thesuspensionswereliftedandmarketinglicencesreinstated.157
Asaresultoftherecall,manypatientswerechangedtoanotherPI.ItisunknowniftherewillcontinuetobedemandfortheNFVformulationinthefuture.NFVwasalsodeletedfromthe16theditionoftheWHOModelListofEssentialMedicines(EML).
PatentsEventhoughpatentscouldnotbeappliedforinIndiapriorto1995,AgouronappliedforpatentsonNFVinmanyotherdevelopingcountries.Thisfactorcontributestothehighpriceofthedrug,togetherwiththesmalldemand.
TherecallofRoche’sNFVin2007highlightstheriskassociatedwithrelyingonasingleproducerforamedicine.
PaediatricsTheuseofNFVoralpowderinchildrenisextremelycomplex.Toobtainthecorrectdosefora10kgchild,12goftheoralpowdermustbemixedwithwater.Accesstoclean,safewaterisoftennotensuredinalldevelopingcountries.
NotonlyisthepaediatricNFVformulationill-adapted,butitspriceremainsprohibitive,asisthecasewithotherproteaseinhibitors.
�0 Médecins Sans Frontières | July 2010
RITONAVIR ( r or RTV )
GENERAL INFORMATION
Evolution of the lowest price quoted for developing countries since �00�:
AsofApril2010,therewasnogenericsourceofRTV100mgsoft-gelcapsuleincludedintheWHOListofPrequalifiedMedicinalProducts.Thelowestavailablegenericpriceisthereforeshownhere.
Oct 01
Dec 02
Jun02
Dec03
May03
Feb05
Apr04
Jun06
Jun05
Jun 07
Jun 08
Dec09
Jun10
US$
pp
y
Month/Year
4000
3500
3000
2500
2000
1500
1000
500
0
lowest originator price
generic price
RTV 100mg capsule (soft-gel)
3504
108323
83
•Includedinthe16theditionoftheWHOModelListofEssentialMedicines(EML).26
•Worldsalesoforiginatorproduct:2004:US$194million;2003:$93million;and2002:$122million.158After2004,therearenosalesfigureslistedinthecompany’sannualreport.
•ThebasicpatentwasappliedforbyAbbottin1993.159Subsequently,AbbottappliedforpatentsrelatedtopolymorphicformsofRTV 149,160andtoasoft-gelcapsuleformulation.161Theseareduetoexpirerespectivelyin2019and2020.
PRICE INFORMATIONDeveloping country prices in US$ per patient per year, as quoted by companies. Thepriceinbracketscorrespondstothepriceofonecapsule/tablet/doseoforalsolution.ProductsincludedintheWHOListofPrequalifiedMedicinalProducts(asofApril2010)areinbold.
•Therapeuticclass:proteaseinhibitor(PI).
•Indicatedforsecond-lineasabooster,foradults,adolescentsandchildren.8,137
•Originatorcompanyandproductbrandname:AbbottLaboratories,Norvir.
•FirstapprovalbyU.S.FoodandDrugAdministration(FDA):March1996fortheoralsolutionandJune1999forcapsules.17
RIT
ON
AV
IR (
r o
r R
TV
)P
RO
TE
ASE
IN
HIB
ITO
RS (
PI )
Dailydose,usedasbooster
Abbott Cipla
Whocanaccessthisprice? Seeannex2&annex8 Norestrictions
RTV80mg/mloralsolution - (0.093/ml)
RTV100mgsoft-gelcapsule 2 83 (0.114)
323(0.442)
RTV100mgheat-stabletablet 283(0.114)
Untangling the Web of ARV Price Reductions | Please check utw.msfaccess.org ��
RIT
ON
AV
IR ( r
or R
TV
)P
RO
TE
ASE
INH
IBIT
OR
S ( P
I )
SPOTLIGHT ON ACCESS ISSUES
Ritonavir(RTV)isofcrucialimportanceforthescaling-upandmanagementofsecond-linetreatment,asallproteaseinhibitors(PIs)(withtheexceptionofnelfinavir(NFV)),mustbeboostedwiththisdrug.
Abbotthasdevelopedaheat-stablefixed-dosecombinationoflopinavirandRTV(LPV/r)thatwasapprovedintheU.S.in2005.However,ittookuntilearly2010forAbbotttofinallyreceiveU.S.FDAandEMAapprovalforaheat-stableformulationofRTV100mgtablet,12yearsafterRTVsoft-gelcapsulefirstreceivedregulatoryapproval.
Themarketauthorisationofaheat-stableversionofritonavirasaseparatepillfinallyendsboththestrangleholdbyAbbottonthetreatmentoptionsavailabletopeoplelivingwithHIV/AIDSandthemedicaldoublestandardsthecompanyhaspromotedbyfailingtoprioritisethedevelopmentofsaferversionsofitsmedicines.AsaresultofAbbott’sinaction,manypeoplelivingwithHIVhavebeendeprivedofadditional,improvedandvitaltreatmentoptionsformanyyears.
TheregistrationofthisnewformulationindevelopingcountrieswillbecrucialtoallowtheuseofotherPIsthanlopinavir.
Patents
AlthoughthebasicpatentdisclosingRTVcouldnotbeappliedforinIndia,Abbott’soriginalpatentapplicationsanddivisionalapplicationsonnewformsofRTVarependingbeforetheIndianpatentoffice.Apre-grantoppositiontoanapplicationrelatedtoapolymorphofRTVwasfiledbycivilsocietyorganisationsinIndiainSeptember2006.151ThedecisionoftheIndianpatentofficeispending.TheoutcomeofthisoppositionwillbecrucialtothemanagementofPI-basedsecond-linetreatment.
PatentsrelatedtopolymorphicformsofRTVhavealsobeenfiledinothermiddle-incomecountriessuchasChinaandBrazilwheretheyarepending.InBrazil,ritonavirislocallyproduced,asthebasicpatentisbeingopposedbyBraziliangenericmanufacturersintheCourts.
On14April2010,EcuadorissueditsfirstcompulsorylicenceallowingEskegroupSA,thelocaldistributorforCipla,tomanufacture,offerforsale,sell,useorimportRTV,orcompositionsincludingRTV,forpublicnon-commercialuse,againstthepaymentofroyaltiestoAbbott,untilthepatentexpirationdatein2014.162
ThecompulsorylicencefollowedadecreeofEcuadorianPresidentRafaelCorreainOctober2009,declaringaccesstoessentialmedicinesofpublicinteresttotheEcuadoreanpopulationandallowingthenationalintellectualpropertyofficetoissuecompulsorylicencestothisend,basedonArticle31oftheTRIPSAgreement.163
AccordingtotheMinistryofHealth,thecompulsorylicencealreadyhasyieldedsavingsofUS$150,000tothegovernment.
PaediatricsRTVisapprovedforuseinchildrenandthereisaliquidformulationavailable.Thesolutionhasabitteraftertasteandis43%alcohol,andhencenotadaptedforchildren.
ThePaediatricAntiretroviralWorkingGroupofWHOconsidersthedevelopmentofaRTV50mgheat-stablesprinkleortablettobeahighpriority.137
�� Médecins Sans Frontières | July 2010
GENERAL INFORMATION
•Therapeuticclass:proteaseinhibitor(PI).
•NotcurrentlyincludedinWHOguidelines.
•Originatorcompanyandproductbrandname:Roche,Invirase.
Evolution of the lowest price quoted for developing countries since �00�:
AsofApril2010,therewasnogenericsourceofSQV200mghardcapsuleincludedintheWHOListofPrequalifiedMedicinalProducts.Thelowestavailablegenericpriceisthereforeshownhere.
RochequotespricesinSwissFrancs(CHF),whichhavebeenconvertedtoUS$onthedatereceived.FluctuationsintheUS$/CHFratewillthushaveanimpactonpricesusedinthegraph.
SAqUINAVIR ( SqV )
Jun02
Dec 02
Dec03
May03
Feb05
Apr04
Jun06
Jun05
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Jun 08
Dec09
Jun10
US$
pp
y
Month/Year
2000
1800
1600
1400
1200
1000
800
600
400
200
0
lowest originator price
generic priceSQV 200mg hard capsule
13421212
1335
1621
•FirstapprovalbyU.S.FoodandDrugAdministration(FDA):December1995.17
•Includedinthe16theditionoftheWHOModelListofEssentialMedicines(EML).26
•Worldsalesoforiginatorproduct:therearenosalesfigureslistedinthecompany’sannualreport.
•ThebasicpatentwasappliedforbyRochein1990164andisduetoexpireinDecember2010incountriesnotgrantingpatentextensions.
•ApatentrelatedtooraldosageformwasappliedbyRochein2004andisduetoexpirein2024.165
PRICE INFORMATIONDeveloping country prices in US$ per patient per year, as quoted by companies. Thepriceinbracketscorrespondstothepriceofonecapsule/tablet.ProductsincludedintheWHOListofPrequalifiedMedicinalProducts(asofApril2010)areinbold.
Dailydose
Roche
CiplaCategory1countries
Category2countries
Whocanaccessthisprice? Seeannex2 Norestrictions
SQV200mghardcapsule 10* 1212 (0.332)
2427 (0.665)
1621(0.444)
SQV500mgtablet 4* 1113 (0.762)
2427 (1.662)
*ThedoseofSQVmustbeboostedwithRTV100mgtwiceaday.
SA
qU
INA
VIR
( S
qV
)P
RO
TE
ASE
IN
HIB
ITO
RS (
PI )
Untangling the Web of ARV Price Reductions | Please check utw.msfaccess.org ��
SPOTLIGHT ON ACCESS ISSUES
InDecember2009,WHOrecommendationsforsecond-linetherapyincludedtwo‘preferred’proteaseinhibitors(PI),tobetakenincombinationwithtwoNRTIs.Theyareatazanavir(ATV)boostedwithritonavir(RTV)andlopinavir/ritonavir(LPV/r).Assaquinavir(SQV)wasnotidentifiedasoneofthepriorityproducts,itsuseinthedevelopingworldwillbelimited.9
SQV/rappearstobeslightlylesspotentthantheotherboostedPIsandintheoriginalformulationhasahighpillcount(10capsules).141In2004,Rochemarketeda500mgtabletofSQVintheU.S.thatreducedthepillcountfrom10tabletstofour.Whilethisnewformulationshouldimproveadherence,itisonlyregisteredandmarketedinselecteddevelopingcountries.
Aswithotherproteaseinhibitors,SQV’shighpricecontinuestobeabarrier.Solidcompetitionandeconomiesofscaleamongproducersareminimal,asitsuseisfairlylimited.
SQV,likeallPIs(withtheexceptionofnelfinavir(NFV)),requiresboostingwithritonavir(RTV).Abbott’sheat-stableritonavirreceivedmarketingapprovalintheU.S.andEuropeinearly2010.RegisteringthisnewformulationindevelopingcountrieswillbecrucialinordertoallowtheuseofotherPIsthanlopinavir.
TherequiredadditionofRTVasaboostermustalsobeconsideredinthefinalcostofusingSQV.
PatentsThebasicpatentwasrejectedinBrazilwherethismedicineislocallyproduced.ItwashowevergrantedinmanyothercountriesincludingChina,SouthAfricaandOAPIcountries.
PatentsrelatedtotheoraldosageformarependinginBrazilandChina.TheyhavebeengrantedinIndiaandSouthAfrica.
PaediatricsSQVhasnotbeenapprovedforuseinchildrenintheU.S.andthereisnopaediatricformulationavailable.
SA
qU
INA
VIR
( Sq
V )
PR
OT
EA
SE
INH
IBIT
OR
S ( P
I )
Médecins Sans Frontières | July 2010
TIP
RA
NA
VIR
( T
PV
)P
RO
TE
ASE
IN
HIB
ITO
RS (
PI )
TIPRANAVIR ( TPV )
GENERAL INFORMATION
SPOTLIGHT ON ACCESS ISSUES
InDecember2009,WHOrecommendationsforsecond-linetherapyincludedtwo‘preferred’proteaseinhibitors(PI),tobetakenincombinationwithtwoNRTIs.Theyareatazanavir(ATV)boostedwithritonavir(RTV)andlopinavir/ritonavir(LPV/r).Astipranavir(TPV)wasnotidentifiedasoneofthepriorityproducts,itsuseinthedevelopingworldwillbelimited.9
BoehringerIngelheimwasinvitedtocontributeapriceforthispublicationandhascommunicatedthattipranavir(TPV)isavailablethroughitsCompassionateUseProgramandthatthecompanyiscurrentlyfilingforregistrationinvariouscountries.
TPV,likeallPIs(withtheexceptionofnelfinavir(NFV)),requiresboostingwithritonavir(RTV).Abbott’sheat-stableritonavirreceivedmarketingapprovalintheU.S.andEuropeinearly2010.
RegisteringthisnewformulationindevelopingcountrieswillbecrucialinordertoallowtheuseofotherPIsthanlopinavir.
TherequiredadditionofRTVasaboostermustalsobeconsideredinthefinalcostofusingTPV.
OnefurtherlimitationconcerningTPVisthatthecapsulesrequirerefrigerationuntildispensing.
Patents
TPVpatentshavebeenfiledforwidelyindevelopingcountrieswithgenericproductioncapacity,suchasBrazilandChina.39
InBrazil,wherethepatentapplicationsareunderreview,thedrugregulatoryagency(ANVISA),whichhastogive‘priorconsent’foranypatentapplicationrelatedtoamedicine,hasadvisedfortherejectionofthebasicpatentapplication.170
Inearly2007,civilsocietyexpressedconcernsoverthedelaystotheregistrationprocedureofTPVinBrazil(themedicinehadbeentestedinBrazilianpatientsin14researchcentressinceFebruary2004,butthedrugwasnotactuallyregisteredinthecountry).Afterconsiderablecivilsocietypressure,theregistrationwaseventuallyfiledwithANVISAattheendofFebruary2008,almostthreeyearsafterU.S.FDAandEMAapprovals.TheinterventionbyBraziliancivilsocietywaspartlybasedinresponsetosuspicionsthatBoehringerIngelheimdidnotwanttoregistertheproductinthecountry,unlesstheyhadtheguaranteethatthepatentwouldbegrantedbythepatentoffice.171,172
Paediatrics
TPViscurrentlyapprovedforuseinchildrenfromtwoyearsofageandolder,andapaediatricoralsolutionexists.17
PRICE INFORMATIONBoehringer Ingelheim was invited to contribute a price for this publication and has communicated it does not offer a reduced price for developing countries.
•Therapeuticclass:ProteaseInhibitor(PI).
•NotcurrentlyincludedinWHOguidelines.
•TPVisindicatedforcombinationtreatmentofHIV-1infectedadultpatientswhoaretreatment-experiencedandinfectedwithHIV-1strainsresistanttomorethanoneproteaseinhibitor.166
•Originatorcompanyandproductbrandname:BoehringerIngelheim(BI)Pharmaceuticals,Aptivus.
•FirstapprovedbytheU.S.FoodandDrugAdministration(FDA):June2005.17
•Notincludedinthe16theditionoftheWHOModelListofEssentialMedicines(EML).26
•Worldsalesoforiginatorproduct:therearenosalesfigureslistedinthecompany’sannualreport.
•ThebasicpatentwasappliedforbyUpjohninMay1995,167andisduetoexpirein2015.In1998,Pharmacia&UpjohnappliedforadditionalpatentsrelatedtopharmaceuticalformulationssuitablefortheoraladministrationofTPV.168,169InJanuary2000,BIacquiredworldwiderightsforTPV.
��
Untangling the Web of ARV Price Reductions | Please check utw.msfaccess.org
GENERAL INFORMATION
ABACAVIR/ LAMIVUDINE ( ABC/�TC )
Dailydose
ViiV Aurobindo(CF) Cipla Matrix(CF)
Whocanaccessthisprice? Seeannex2 Norestrictions
ABC/3TC60/30mgtablet 4 175 (0.120)
244 (0.167)
ABC/3TC600/300mgtablet 1484(1.326)
134 (0.367)
152(0.417)
Continued overleaf
PRICE INFORMATIONDeveloping country prices in US$ per patient per year, as quoted by companies. Thepriceinbracketscorrespondstothepriceofonetablet.ProductsincludedintheWHOListofPrequalifiedMedicinalProducts(asofApril2010)areinbold.
•Therapeuticclass:doublefixed-dosecombinationoftwoNRTIs.
•Indicatedforfirst-andsecond-lineforchildrenandaspartoftripleNRTIdrugsunderspecificconditionsinadults,adolescentsandchildren.8,137
•Originatorcompany,andproductbrandname:GlaxoSmithKline(GSK),Kivexa(EU),Epzicom(U.S.).InApril2009,PfizerandGSKjointlyannouncedthecreationofViiV,anewjoint
venturefocusingsolelyontheR&DandcommercialisationofHIVmedicines.
•FirstapprovalbyU.S.FoodandDrugAdministration(FDA):August2004.17
•TheWHOExpertCommitteeontheSelectionandUseofEssentialMedicinesrecommendsandendorsestheuseoffixed-dosecombinationsandthe
developmentofappropriatenewfixed-dosecombinations.26
•Worldsalesoforiginatorproduct:2009:US$834million;2008:$721million;2007:$641million;2006:$475million;2005:$233million.77,79,80,81,82
•Mostpatentsonabacavir(ABC)orlamivudine(3TC)alsoaffectthiscombination.Inaddition,GSKappliedforpatentsmorespecificallyrelatedtothecombination.173Thepatentexpirydatesrelatedtothiscombinationare2016intheU.S.and2019inEU.82
AB
AC
AV
IR/L
AM
IVU
DIN
E ( A
BC
/�
TC
)F
IxE
D-D
OSE
CO
MB
INA
TIO
NS A
ND
CO
-PA
Ck
S
��
(CF)TheClintonFoundationhasnegotiatedwiththismanufacturerforreducedpricesonsomeformulationsforcountriesintheirconsortium.Seeannex13fordetails.
Evolution of the lowest price quoted for developing countries since �00�:
AsofApril2010,therewasonegenericsourceofABC/3TC600/300mgtabletincludedintheWHOListofPrequalifiedMedicinalProducts.Itspriceisshownhere.
Therehasbeenadecreaseof47%inthegenericpricesince2006.
Jun 06 Jun 07 Jun 08 Jun 10Dec 09
US$
pp
y
Month/Year
800
700
600
500
400
300
200
100
0
lowest originator price
generic price
ABC/3TC 600/300mg tablet
255
678
134
484
Médecins Sans Frontières | July 2010
AB
AC
AV
IR/L
AM
IVU
DIN
E (
AB
C/�
TC
)F
IxE
D-D
OSE
CO
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INA
TIO
NS A
ND
CO
-PA
Ck
S
��
SPOTLIGHT ON ACCESS ISSUES
ThiscombinationislikelytofalloutoffavoursincethelatestWHOguidelinesforadultsandadolescentsrecommendalineconsistingofeitherAZTorTDF.ItremainsanimportantcombinationforthetreatmentofpaediatricHIV,however.
PatentsGlaxoSmithKlinecouldnotapplyforbasicpatentsrelatedtoabacavir(ABC)orlamivudine(3TC)insomedevelopingcountriessuchasIndiathatdidnotgrantpatentsonpharmaceuticalproductsatthetime.ThisallowedIndiandrugmanufacturerstodevelopgenericversionsofeachmedicine,andofthecombinationofthetwo.
However,GSKwidelyappliedforpatentsinotherdevelopingcountrieswherepossible.
PaediatricsThePaediatricAntiretroviralWorkingGroupofWHOconsidersthedevelopmentofascoredadultfixed-dosecombinationofABC/3TC300/150mgtablet,foruseinchildrenweighingover25kg,tobeahighpriority.137
ViiVdoesnotproduceafixed-dosecombinationofthesedrugsforchildren–eventhoughtheFDCsexistforadults.Nevertheless,forchildrenwhoneedthiscombination,therearetwogenericsourcesincludedintheWHOListofPrequalifiedMedicinalProducts.
ThePaediatricAntiretroviralWorkingGroupofWHOalsoconsidersthedevelopmentofatriplefixed-dosecombinationofabacavir/lamivudine/nevirapine60/30/50mgtablettobeahighpriority.137
Abacavir/Lamivudine ( ABC/3TC ) continued
Untangling the Web of ARV Price Reductions | Please check utw.msfaccess.org
LAMIVUDINE/ STAVUDINE ( �TC/d�T )
GENERAL INFORMATION
•Therapeuticclass:doublefixed-dosecombinationoftwoNRTIs.
•Indicatedforfirst-lineinchildrenanditisrecommendedtomoveawayfromd4Tinfirst-lineinadultsandadolescents.8,137
•WHOupdatedthe2006guidelinestorecommendareductionindoseofd4Tfrom40to30mgforallweightcategoriesofpatients.107
•TheWHOExpertCommitteeon
theSelectionandUseofEssential
Medicinesrecommendsandendorses
theuseoffixed-dosecombinations
andthedevelopmentofappropriate
newfixed-dosecombinations.26
•Includedinthe16theditionWHO
ModelListofEssentialMedicines
(EML)–onlythed4T30mg
presentation.26
•Individualpatentsonlamivudine(3TC)orstavudine(d4T)alsoaffectthiscombination.Inaddition,otherpatentsmayhavebeenappliedformorespecificallyrelatedtotheuseofbothmedicinesincombination,ortotheFDC.
PRICE INFORMATIONDeveloping country prices in US$ per patient per year, as quoted by companies. Thepriceinbracketscorrespondstothepriceofonetablet.ProductsincludedintheWHOListofPrequalifiedMedicinalProducts(asofApril2010)areinbold.
��
LA
MIV
UD
INE
/ST
AV
UD
INE
( �T
C/d
�T
)F
IxE
D-D
OSE
CO
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NS A
ND
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-PA
Ck
S
Continued overleaf
Evolution of the lowest price quoted for developing countries since �00�:
AsofApril2010,thereweresixgenericsourcesof3TC/d4T150/30mgtabletincludedintheWHOListofPrequalifiedMedicinalProducts.Theonewiththelowestpriceisshownhere.Asthereisnooriginatorfixed-dosecombination,thepriceshownfortheoriginatorproductisthesumofthetwoindividualoriginatorproducts.
Therehasbeena39%decreaseintheoriginatorpriceanda66%decreaseingenericpricesince2003.
Dec03
May03
Feb05
Apr04
Jun06
Jun05
Jun 07
Jun 08
Dec09
Jun10
US$
pp
y
Month/Year
200
180
160
140
120
100
80
60
40
20
0
lowest originator price
generic price
3TC/d4T 150/30mg tablet
42
112125
183
(CF)TheClintonFoundationhasnegotiatedwiththismanufacturerforreducedpricesonsomeformulationsforcountriesintheirconsortium.Seeannex13fordetails.
Dailydose
Aurobindo(CF) Cipla(CF) Hetero Matrix(CF) Ranbaxy Strides
Whocanaccessthisprice? Norestrictions
3TC/d4T30/6mgdispersibletablet 4 47 (0.032)
3TC/d4T60/12mgdispersibletablet 2 40 (0.055)
3TC/d4T150/30mgtablet 2 50 (0.068)
42 (0.057)
51(0.070)
42 (0.058)
42 (0.058)
44 (0.060)
Médecins Sans Frontières | July 2010
SPOTLIGHT ON ACCESS ISSUES
Thiscombinationhasbeenanimportantformulationthathasfosteredtreatmentscale-upinresource-limitedsettings.
InDecember2009,WHOreleasednewrecommendationsforantiretroviraltherapyforHIVinadultsandadolescents.Thesenewrecommendationsadvisecountriestophaseoutstavudine-basedregimensbecauseoftheirlong-termirreversiblesideeffectsandtomovetowardszidovudine(AZT)ortenofovir-based(TDF)first-lineregimens.9
Lamivudine/Stavudine ( 3TC/d4T ) continued
��
LA
MIV
UD
INE
/ST
AV
UD
INE
( �
TC
/d
�T
)F
IxE
D-D
OSE
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ND
CO
-PA
Ck
S
Wecanthereforeexpecttoseeadecreaseintheuseofthisformulationinthefuture.
PatentsGenericcompaniesincertaindevelopingcountrieswereabletodevelopthesefixed-dosecombinationsbecausepatentsontheindividualproductsdidnotexist.
Thefixed-dosecombinationisnotavailableindevelopedcountriesorincountriessuchasChina,however,whereoneorbothmedicinesisunderpatent.
Paediatrics
Themostcommonlyusedfirst-
lineregimensforchildrentoday
areeither3TC+d4T+NVPor
AZT+3TC+NVP.Withbothofthese
regimens,thereisaneedtostart
nevirapine(NVP)atalowerdose
forthefirsttwoweekstominimise
thesideeffects.
Forchildrenwhoneedthisdouble
3TC/d4Tfixed-dosecombination,
therearetwogenericproducts
includedintheWHOListof
PrequalifiedMedicinalProducts.
Untangling the Web of ARV Price Reductions | Please check utw.msfaccess.org
LA
MIV
UD
INE
/ST
AV
UD
INE
/N
EV
IRA
PIN
E ( �
TC
/d
�T
/N
VP
)
Evolution of the lowest price quoted for developing countries since �00�:
AsofApril2010,therewereninegenericsourcesof3TC/d4T/NVP150/30/200mgtabletincludedintheWHOListofPrequalifiedMedicinalProducts.Theonewiththelowestpriceisshownhere.Asthereisnooriginatorfixed-dosecombination,thepriceshownfortheoriginatorproductisthesumofthethreeindividualoriginatorproducts.
Therehasbeenadecreaseof76%inthegenericpricesince2002.
LAMIVUDINE/STAVUDINE/ NEVIRAPINE ( �TC/d�T/NVP )
GENERAL INFORMATION
•Therapeuticclass:triplefixed-dosecombinationoftwoNRTIsandaNNRTI.
•Indicatedforfirst-lineforchildrenanditisrecommendedtomoveawayfromd4T-basedfirst-lineinadultsandadolescents.8,137
•WHOupdatedthe2006guidelinestorecommendareductionindoseofd4Tfrom40to30mgforallweightcategoriesofpatients.107
•Includedinthe16theditionoftheWHOModelListofEssentialMedicines(EML)–onlythed4T30mgpresentation.26
•TheWHOExpertCommitteeontheSelectionandUseofEssentialMedicinesrecommendsandendorsestheuseoffixed-dosecombinationsandthedevelopmentofappropriatenewfixed-dosecombinations.26
•Individualpatentsonlamivudine(3TC),stavudine(d4T)ornevirapine(NVP)alsoaffectthiscombination.Inaddition,otherpatentsmayhavebeenappliedformorespecificallyrelatingtotheuseofthemedicinesincombinationortothefixed-dosecombination.CiplafirstdevelopedtheFDCandappliedforpatentsinseveralAfricancountries.
PRICE INFORMATIONDeveloping country prices in US$ per patient per year, as quoted by companies. Thepriceinbracketscorrespondstothepriceofonetablet.ProductsincludedintheWHOListofPrequalifiedMedicinalProducts(asofApril2010)areinbold.
Dec 02
Jun02
Dec03
May03
Feb05
Apr04
Jun06
Jun05
Jun 07
Jun 08
Dec09
Jun10
US$
pp
y
Month/Year
700
600
500
400
300
200
100
0
lowest originator price
generic price
3TC/d4T/NVP 150/30/200mg tablet
67
281331
615
(CF)TheClintonFoundationhasnegotiatedwiththismanufacturerforreducedpricesonsomeformulationsforcountriesintheirconsortium.Seeannex13fordetails.
FIx
ED
-DO
SE
CO
MB
INA
TIO
NS A
ND
CO
-PA
Ck
S
��
Continued overleaf
Dailydose
Aurobindo(CF) Cipla(CF) Hetero(CF) Matrix(CF) Ranbaxy Strides
Whocanaccessthisprice? Norestrictions
3TC/d4T/NVP30/6/50mgdispersibletablet
4 55 (0.038)
3TC/d4T/NVP60/12/100mgdispersibletablet
2 53 (0.072)
3TC/d4T/NVP150/30/200mgtablet
2 67 (0.092)
67 (0.092)
73 (0.100)
67 (0.092)
70 (0.096)
73 (0.100)
Médecins Sans Frontières | July 2010
SPOTLIGHT ON ACCESS ISSUES
ThiscombinationislikelytofalloutoffavoursincethelatestWHOadultsandadolescentsguidelinesrecommendedanAZT-orTDF-basedfirst-lineregime.
InDecember2009,WHOreleasednewrecommendationsforantiretroviraltherapyforHIVinadultsandadolescents.Thesenewrecommendationsadvisecountriestophaseoutstavudine-basedregimensbecauseoftheirlong-termirreversiblesideeffectsanddevelopaplantomovetowardszidovudine(AZT)ortenofovir-based(TDF)first-lineregimens.9
Wecanthereforeexpecttoseeadecreaseintheuseofthisformulationinthefuture.
PatentsCiplawasabletodevelopthiscombinationbecausenoneoftheindividualcomponentswerepatentedinIndia.Manyothergenericmanufacturershavefollowedsuitinotherdevelopingcountries,suchasThailand,wherethemedicineswerenotpatented.
ExtensivecompetitionfromnumerousgenericmanufacturershasmadethiscombinationthemostaffordabletripleARVcombinationtreatmenttodate.
PaediatricsThisisoneofthemost-commonlyusedfirst-lineregimensforchildrentoday.
ThePaediatricWorkingGroupatWHOhasreleasedclearguidanceontheidealstrengthofeachoftheindividualARVsinthesefixed-dosecombinations,andtodaytherearetwoformulationsincludedonWHOListofPrequalifiedMedicinalProducts.90
Lamivudine/Stavudine/Nevirapine ( 3TC/d4T/NVP ) continued
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Evolution of the lowest price quoted for developing countries since �00�:
AsofApril2010,therewasonegenericsourceof3TC/d4T+EFV150/30+600mgco-packincludedintheWHOListofPrequalifiedMedicinalProducts.Itspriceisshownhere.Asthereisnooriginatorco-pack,thepriceshownfortheoriginatorproductisthesumofthethreeindividualoriginatorproducts.
Thecombinedpriceoftheoriginatorproductsfor3TC/d4T+EFV150/30+600mghasdecreasedby11%since2006.Thegenericco-packincludedintheWHOListofPrequalifiedMedicinesisafurther13%cheaperthanthesumoforiginatorproducts.
LAMIVUDINE/STAVUDINE + EFAVIRENZ ( �TC/d�T + EFV )
GENERAL INFORMATION
•Therapeuticclass:twoNRTIs+oneNNRTIinaco-pack.
•Indicatedforfirst-lineforchildrenanditisrecommendedtomoveawayfromd4Tbasedfirst-lineinadultsandadolescents.8,137
•WHOupdatedthe2006guidelinestorecommendareductionindoseof
(CF)TheClintonFoundationhasnegotiatedwiththismanufacturerforreducedpricesonsomeformulationsforcountriesintheirconsortium.Seeannex13fordetails.
SPOTLIGHT ON ACCESS ISSUES
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d4Tfrom40to30mgforallweightcategoriesofpatients.107
•IncludedintheWHOModelListofEssentialMedicines(EML)-onlythed4T30mgpresentation.26
•TheWHOExpertCommitteeontheSelectionandUseofEssentialMedicinesrecommendsandendorsestheuseoffixed-dosecombinations
andthedevelopmentofappropriatenewfixed-dosecombinations.26
•Individualpatentsonlamivudine(3TC),stavudine(d4T)orefavirenz(EFV)alsoaffectthiscombination.Inaddition,otherpatentsmayhavebeenappliedformorespecificallyrelatedtotheuseofthemedicinesincombination,ortotheFDC.
Jun 06 Jun 07 Jun 08 Dec 09 Jun 10
US$
pp
y
Month/Year
450
400
350
300
250
200
lowest originator price
generic price
3TC/d4T + EFV 150/30 + 600mg co-pack
394
274
349
304
InDecember2009,WHOreleased
newrecommendationsfor
antiretroviraltherapyforHIVin
adultsandadolescents.Thesenew
recommendationsadvisecountriesto
phaseoutstavudine-basedregimens
becauseoftheirlong-termirreversible
sideeffectsandtomovetowards
zidovudine(AZT)ortenofovir(TDF)-basedfirst-lineregimens.9
Wecanthereforeexpecttoseeadecreaseintheuseofthisformulationinthefuture.
PatentsGenericcompaniesincertaindevelopingcountrieswere
abletodevelopthisco-blisterbecausepatentsontheindividualcomponentscontainedinthecombinationdidnotexist.
ThisproductisthusnotavailableindevelopedcountriesorinChinabecauseofvariouspatentson3TC,d4Tand/orEFV.
Dailydose Cipla(CF) Ranbaxy Strides(CF)
Whocanaccessthisprice? Norestrictions
3TC/d4T+EFV150/30+600mgtablets(co-pack)
1kit(3tablets)
274(0.751)
304 (0.833)
106(0.290)
PRICE INFORMATIONDeveloping country prices in US$ per patient per year, as quoted by companies. Thepriceinbracketscorrespondstothepriceofonekit(3tablets).ProductsincludedintheWHOListofPrequalifiedMedicinalProducts(asofApril2010)areinbold.
Médecins Sans Frontières | July 2010
TENOFOVIR DISOPROxIL FUMARATE/EMTRICITABINE ( TDF/FTC )
GENERAL INFORMATION
•Therapeuticclass:oneNtRTI+oneNRTIinadoublefixed-dosecombination.
•Indicatedforfirst-lineandsecond-lineforadultsandadolescents.8
•Originatorcompanyandproductbrandname:Gilead,Truvada.
•FirstapprovalbyU.S.FoodandDrugAdministration(FDA):August2004.17
Evolution of the lowest price quoted for developing countries since �00�:
AsofApril2010,thereweretwogenericsourcesofTDF/FTC300/200mgtabletincludedintheWHOListofPrequalifiedMedicinalProducts.Theonewiththelowestpriceisshownhere.
Since2007,therehasbeena48%decreaseinthegenericprice.
US$
pp
y
Month/Year
400
350
300
250
200
150
100
50
0Feb05
Jun06
Jun05
Jun 07
Jun 08
Dec09
Jun10
lowest originator price
generic price
TDF/FTC 300/200mg tablet
362
315
274
143
•Includedinthe16theditionoftheWHOModelListofEssentialMedicines(EML).26
•TheWHOExpertCommitteeontheSelectionandUseofEssentialMedicinesrecommendsandendorsestheuseoffixed-dosecombinationsandthedevelopmentofappropriatenewfixed-dosecombinations.26
•Worldsalesoforiginatorproduct:2009:US$2.49billion;2008:$2.11billion;2007:$1.59billion;2006:$1.19billion;2005:$568million;2004:$68million.93,96
•Mostpatentsrelatedtotenofovir(TDF)ortoemtricitabine(FTC)alsoaffectthiscombination.Inaddition,Gileadappliedforpatentsspecificallyrelatedtothiscombinationin2004,whichareduetoexpirein2024.58
PRICE INFORMATIONDeveloping country prices in US$ per patient per year, as quoted by companies. Thepriceinbracketscorrespondstothepriceofonetablet.ProductsincludedintheWHOListofPrequalifiedMedicinalProducts(asofApril2010)areinbold.
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Gilead
Aurobindo(CF) Cipla Hetero Matrix(CF)Category1countries
Category2countries
Whocanaccessthisprice? Seeannex2&annex9 Norestrictions
TDF/FTC300/200mgtablet 1 315 (0.863)
540 (1.479)
155 (0.425)
158(0.433)
164(0.450)
143 (0.392)
(CF)TheClintonFoundationhasnegotiatedwiththismanufacturerforreducedpricesonsomeformulationsforcountriesintheirconsortium.Seeannex13fordetails.
Untangling the Web of ARV Price Reductions | Please check utw.msfaccess.org
SPOTLIGHT ON ACCESS ISSUES
Thiscombinationislikelytobewidelyusedindevelopingcountriesasabackboneinfirst-andsecond-lineregimens.
InDecember2009,WHOreleasednewrecommendationsforantiretroviraltherapyforHIVinadultsandadolescents.Thesenewrecommendationsadvisecountriestophaseoutstavudine-basedregimensbecauseoftheirlong-termirreversiblesideeffectsandtomovetowardszidovudine(AZT)ortenofovir-based(TDF)first-lineregimens.9
Formanyyears,thestavudine-containing(d4T)regimenhasplayedacrucialroleinARTscale-upinresource-limitedsettings,duetoitsavailabilityinafixed-dosecombinationandmostimportantlyitslowcost.d4Tremainsawidely-usedARVinfirst-lineregimens.
Itishowevertimeforcountriestoinvestinamorerobust,TDF-basedfirst-lineregimen,suchasTDF/3TC/EFVorTDF/FTC/EFV,whichisonepillonceaday.Whilethepricetodayisstillhigherthanad4T-basedregimen,thereisaneedtogenerategreaterdemandwhichwill,inturn,increasethecompetitionneededtofurtherdecreaseprices.9
Forsecond-linetreatment,TDFincombinationwithlamivudine(3TC)oremtricitabine(FTC)aretherecommendedNRTIbackbones,tobeaddedtoaboostedproteaseinhibitor,ifstavudineorzidovudinehavebeenusedinthefirst-lineregimen.
TDFisalsoactiveagainstHepatitisBVirus(HBV)andthereforeplaysanimportantroleinco-infectedpatients.ForHIVpatientsalsorequiringtreatmentforHepatitisB,thefirst-andsecond-linetreatmentshouldcontainTDFandeither3TCorFTC.
Today,therearetwogenericsourcesofthiscombinationincludedintheWHOListofPrequalifiedMedicinalProducts.
Patents
ThiscombinationisproducedbyIndiangenericcompaniesbecauseneitheroftheindividualcomponentsispatentedinIndiatoday.However,GileadhasappliedforpatentsrelatedtoTDF.IfthesepatentsaregrantedinIndia,genericcompetitionforthisproductmaybeaffected.
Inamajorvictoryforaccesstomedicines,theIndianpatentofficerejectedseveralpatentapplicationsrelatingtoTDFinSeptember2009.Thepatentswererejectedonthegroundsthattheylackaninventivestep–theydonotmeettherequirementofenhancedefficacystipulatedunderSection3(d)ofIndia’spatentlaw.Further,combinationsofknownmoleculesarenotpatentableunderIndianpatentlaw.174,175,176
Nevertheless,divisionalapplications(atypeofpatentapplicationwhichcontainsmatterfromapreviouslyfiledapplication)havebeenfiledbyGileadforthisandotherpatentapplications.Thismeansthatalthoughthepatentwasnotgranted,thepatentapplicationsarestillpendingbeforethepatentoffice.116,117
ThesameistrueinBrazil,whereanestimated37,000PLHAareonTDF-basedtherapies.InApril2008,thegovernmentdeclaredtenofovirasamedicineofpublicinterestforpriorityexaminationpurposes.TheNationalInstituteonIndustrialProperty(INPI–Brazilianpatentoffice)publishedthepatentrejectionforTDFon30June2009.However,Gileadhasrequestedadivisional
patent,whichhasbeenopposedbycivilsocietygroups.Inaddition,inJanuary2010,Gileadlaunchedalegalchallengeagainstthepatentoffice’sdecisiontorejectthepatent.
InBrazil,Gileadhasalsofiledapatentapplicationforthefixed-dosecombinationTDF/FTC.Ifthepatentisgranted,genericcompetitionwillbestifledonanyessentialcombinationincludingTDF/FTC,beitasadoublefixed-dosecombinationorasatriplefixed-dosecombination,withforexampleefavirenz,lopinaviroratazanavir.FollowingoppositionstothegrantofitspatentsinIndia,Gileadsignedlicensingagreementswith11genericmanufacturersinIndiaandSouthAfrica,allowingthemtomanufactureandexportgenericversionsofGilead’sproductstoalimitedpre-definedlistofcountries,againstthepaymentofa5%royalty.103
ManufacturersthathavesignedtheseagreementsareunabletosupplycountriessuchasBrazilandChina,leavingthesecountriesunabletobenefitfromcompetitivepricesandimproveaccess.AfternegotiationwithGilead,Brazilistodaypaying$715perpatientperyearfortenofovir,overeighttimesthebestavailablegenericprice.129
Suchlicensingagreementscancontributetoincreasedcompetitionandimprovedaccesstoaffordablemedicines,butshouldalsobeofferedtomanufacturersoutsideIndia,andshouldnotincludegeographicmarketlimitations.
Paediatrics
Tenofovirisapprovedforadolescentsfrom12yearsold.However,nopaediatricfixed-dosecombinationhasbeendevelopedwithtenofovirandemtricitabine.
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Médecins Sans Frontières | July 2010
GENERAL INFORMATION
•Therapeuticclass:oneNtRTI+oneNRTI+oneNNRTIinatriplefixed-dosecombination.
•Indicatedforfirst-lineforadultsandadolescents.8
•Originatorcompaniesandproductbrandname:Gilead/Bristol-MyersSquibb/Merck,Atripla.
•FirstapprovalbyU.S.FoodandDrugAdministration(FDA):July2006.17
•Includedinthe16theditionoftheWHOModelListofEssentialMedicines(EML).26
Evolution of the lowest price quoted for developing countries since �00�:
AsofApril2010,therewasonegenericsourceofTDF/FTC/EFV300/200/600mgtabletincludedintheWHOListofPrequalifiedMedicinalProducts.Itspriceisshownhere.
Oververyshorttime,since2007,thegenericpricehasdecreasedby55%,whiletheoriginatorpricehasremainedthesame. U
S$ p
py
Month/Year
700
600
500
400
300
200
100
0Jun 07 Jun 08 Dec 09 Jun 10
lowest originator price
generic price
TDF/FTC/EFV 300/200/600mg tablet
613613
487
219
TENOFOVIR DISOPROxIL FUMARATE/EMTRICITABINE/EFAVIRENZ (TDF/FTC/EFV)
•TheWHOExpertCommitteeontheSelectionandUseofEssentialMedicinesrecommendsandendorsestheuseoffixed-dosecombinationsandthedevelopmentofappropriatenewfixed-dosecombinations.26
•Worldsalesoftheoriginator:2009:US$2.382billion;2008:$1.572billion;2007:$903million;2006,$164million(theproductenteredthemarketinthethirdquarteroftheyear).96
•Mostpatentsrelatedtotenofovir(TDF),emtricitabine(FTC),TDF/FTCortoefavirenz(EFV)alsoaffectthiscombination.Inaddition,GileadandBMSjointlyappliedforpatentsspecificallyrelatedtothiscombinationin2006,59whichwouldlastuntil2026.
•GileadpaysroyaltiestoBMS(andconsequentlyMerck)fortheEFVportion,originallyownedbyDupontMerck,whichwassubsequentlyacquiredbyBMS.
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PRICE INFORMATIONDeveloping country prices in US$ per patient per year, as quoted by companies. Thepriceinbracketscorrespondstothepriceofonetablet.ProductsincludedintheWHOListofPrequalifiedMedicinalProducts(asofApril2010)areinbold.
Dailydose
Gilead/BMS/Merck
Cipla Matrix(CF)Category1countries
Category2countries
Whocanaccessthisprice? Seeannex2&annex10 Norestrictions
TDF/FTC/EFV300/200/600mgtablet 1 613 (1.680)
1033 (2.830)
268(0.733)
219 (0.600)
(CF)TheClintonFoundationhasnegotiatedwiththismanufacturerforreducedpricesonsomeformulationsforcountriesintheirconsortium.Seeannex13fordetails.
Untangling the Web of ARV Price Reductions | Please check utw.msfaccess.org
ispatentedinIndiatoday.However,GileadhasappliedforpatentsrelatedtoTDF,includingtheonespecificallyrelatedtothiscombination.176IfthesepatentsaregrantedinIndia,genericcompetitionforthisproductmaybeaffected.
Inamajorvictoryforaccesstomedicines,theIndianpatentofficerejectedseveralpatentapplicationsrelatingtoTDFinSeptember2009.Thepatentswererejectedonthegroundsthattheylackaninventivestep–theydonotmeettherequirementofenhancedefficacystipulatedunderSection3(d)ofIndia’spatentlaw.Further,combinationsofknownmoleculesarenotpatentableunderIndianpatentlaw.174,175,176
Nevertheless,divisionalapplications(atypeofpatentapplicationwhichcontainsmatterfromapreviouslyfiledapplication)havebeenfiledbyGileadforthisandotherpatentapplications.Thismeansthatalthoughthepatentwasnotgranted,thepatentapplicationsarestillpendingbeforethepatentoffice.116,117
ThesameistrueinBrazil,whereanestimated37,000PLHAareonTDF-basedtherapies.InApril2008,thegovernmentdeclaredtenofovirasamedicineofpublicinterestforpriorityexaminationpurposes.TheNationalInstituteonIndustrialProperty(INPI)publishedthepatentrejectionforTDFon30June2009.However,Gileadhasalsorequestedadivisionalpatentforthepreviouslyrejectedpatent.Inaddition,inJanuary2010,Gileadlaunchedalegalchallengeagainstthepatentoffice’sdecisiontorejectthepatent.
InBrazil,Gileadhasalsofiledapatentapplicationforthefixed-dosecombinationTDF/FTC.Ifthepatentisgranted,genericcompetitionwillbestifledonanyessentialcombinationincludingTDF/FTC,beitasadoublefixed-dosecombinationorasatriplefixed-dosecombination,withforexampleefavirenz,lopinaviroratazanavir.
FollowingoppositionstothegrantofitspatentsinIndia,Gileadsignedlicensingagreementswith11genericmanufacturersinIndiaandoneinSouthAfrica,allowingthemtomanufactureandexportgenericversionsofGilead’sproductstoalimitedpre-definedlistofcountries,againstthepaymentofa5%royalty.103
ManufacturersthathavesignedtheseagreementsareunabletosupplycountriessuchasBrazilandChina,leavingthesecountriesunabletobenefitfromcompetitivepricesandimproveaccess.AfternegotiationwithGilead,BrazilistodaypayingUS$715perpatientperyearfortenofovir,overeighttimesthebestavailablegenericprice.129
Suchlicensingagreementscancontributetoincreasedcompetitionandimprovedaccesstoaffordablemedicines,butshouldalsobeofferedtomanufacturersoutsideIndia,andshouldnotincludegeographicmarketlimitations.
PaediatricsTenofovirisapprovedforadolescentfrom12yearsold.However,nopaediatricfixed-dosecombinationhasbeendevelopedwithtenofovir,emtricitabineandefavirenz.
SPOTLIGHT ON ACCESS ISSUES
Thisisthefirstone-pill-a-dayfixed-dosecombination,whichmakesitwell-adaptedtoresource-poorsettings.
InDecember2009,WHOreleasednewrecommendationsforantiretroviraltherapyforHIVinadultsandadolescents.Thesenewrecommendationsadvisecountriestophaseoutstavudine-basedregimensbecauseoftheirlong-termirreversiblesideeffectsandtomovetowardszidovudineortenofovir-basedfirst-lineregimens.9
Formanyyears,thestavudine-containing(d4T)regimenhasplayedacrucialroleinARTscale-upinresource-limitedsettings,duetoitsavailabilityinafixed-dosecombinationandmostimportantlyitslowcost.d4Tremainsawidely-usedARVinfirst-lineregimens.
Itistime,however,forcountriestoinvestinamorerobust,TDF-basedfirst-lineregimen,suchasTDF/FTC/EFV(orTDF/3TC/EFV).Whilethepricetodayisstillhigherthanad4T-basedregimen,thereisaneedtogenerategreaterdemandwhichwill,inturn,increasethecompetitionneededtofurtherdecreaseprices.9
Inaddition,efavirenz(EFV)isthepreferredNNRTIforuseinpatientsstartingARTwhileontuberculosistreatment.
Today,thereisonegenericsourceofTDF/FTC/EFVwhichisincludedintheWHOListofPrequalifiedMedicinalProducts.
PatentsThiscombinationisproducedbyIndiangenericcompaniesbecausenoneoftheindividualcomponents
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GENERAL INFORMATION
PRICE INFORMATIONDeveloping country prices in US$ per patient per year, as quoted by companies. Thepriceinbracketscorrespondstothepriceofonetablet.ProductsincludedintheWHOListofPrequalifiedMedicinalProducts(asofApril2010)areinbold.
•Therapeuticclass:NtRTI+NRTIinadoublefixed-dosecombination.
•Indicatedforfirst-andsecond-lineforadultsandadolescents.8
•Includedinthe16theditionoftheWHOModelListofEssentialMedicines(EML).26
•TheWHOExpertCommitteeontheSelectionandUseofEssentialMedicinesrecommendsandendorsestheuseoffixed-dosecombinationsandthedevelopmentofappropriatenewfixed-dosecombinations.26
•Mostpatentsrelatedtotenofovir(TDF)ortolamivudine(3TC)alsoaffectthiscombination.Inaddition,otherpatentsmayhavebeenappliedfor,morespecificallyrelatedtotheuseofthesemedicinesincombination,ortothisspecificFDC,suchasbyCipla.177
Dailydose Cipla Hetero(CF) Matrix(CF)
Whocanaccessthisprice? Norestrictions
TDF/3TC300/300mgtablet 1122(0.333)
128 (0.350)
107 (0.294)
(CF)TheClintonFoundationhasnegotiatedwiththismanufacturerforreducedpricesonsomeformulationsforcountriesintheirconsortium.Seeannex13fordetails.
Evolution of the lowest quoted price for developing countries since �00�:
AsofApril2010,thereweretwogenericsourcesofTDF/3TC300/300mgtabletincludedintheWHOListofPrequalifiedMedicinalProducts.Theonewiththelowestpriceisshownhere.Asthereisnooriginatorfixed-dosecombinationthepriceshownfortheoriginatorproductisthesumofthetwoindividualoriginatorproducts.
Since2006,thegenericpricehasdroppedby90%whilethecombinedoriginatorpriceofthetwoindividualproductshasdecreasedby3%.ThemostaffordablegenericFDCis60%lessexpensivethanthesumoftheoriginatorproducts.
US$
pp
y
Month/Year
1200
1000
800
600
400
200
0Jun 07Jun 06 Jun 08 Dec 09 Jun 10
lowest originator price
generic price
TDF/3TC300/300mg tablet
268276
107
1034
Untangling the Web of ARV Price Reductions | Please check utw.msfaccess.org
SPOTLIGHT ON ACCESS ISSUES
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Thiscombinationislikelytobewidelyusedindevelopingcountriesasabackboneinfirst-andsecond-lineregimens.
InDecember2009,WHOreleasednewrecommendationsforantiretroviraltherapyforHIVinadultsandadolescents.Thesenewrecommendationsadvisecountriestophaseoutstavudine-basedregimensbecauseoftheirlong-termirreversiblesideeffectsandtomovetowardszidovudine(AZT)ortenofovir-based(TDF)first-lineregimens.9
Formanyyears,thestavudine-containing(d4T)regimenhasplayedacrucialroleinARTscale-upinresource-limitedsettings,duetoitsavailabilityinafixed-dosecombinationandmostimportantlyitslowcost.d4Tremainsawidely-usedARVinfirst-lineregimens.
Itishowevertimeforcountriestoinvestinamorerobust,TDF-basedfirst-lineregimen,suchasTDF/3TC/EFVorTDF/FTC/EFV,whichisonepillonceaday.Whilethepricetodayisstillhigherthanad4T-basedregimen,thereisaneedtogenerategreaterdemandwhichwill,inturn,increasethecompetitionneededtofurtherdecreaseprices.9
Forsecond-linetreatment,TDFincombinationwithlamivudine(3TC)oremtricitabine(FTC)aretherecommendedNRTIbackbones,tobeaddedtoaboostedproteaseinhibitor,ifstavudineorzidovudinehavebeenusedinthefirst-lineregimen.
TDFisalsoactiveagainstHepatitisBVirus(HBV)andthereforeplaysanimportantroleinco-infectedpatients.ForHIVpatientsalsorequiringtreatmentforHepatitisB,thefirst-andsecond-linetreatmentshouldcontainTDFandeither3TCorFTC.
Today,therearetwogenericsourcesofthiscombinationincludedintheWHOListofPrequalifiedMedicinalProducts.
PatentsThiscombinationisproducedbyIndiangenericcompaniesbecausenoneoftheindividualcomponentsispatentedinIndiatoday.However,GileadhasappliedforpatentsrelatedtoTDF.IfthesepatentsaregrantedinIndia,genericcompetitionforthisproductmaybeaffected.
Inamajorvictoryforaccesstomedicines,theIndianpatentofficerejectedseveralpatentapplicationsrelatingtoTDFinSeptember2009.Thepatentswererejectedonthegroundsthattheylackaninventivestep–theydonotmeettherequirementofenhancedefficacystipulatedunderSection3(d)ofIndia’spatentlaw.Further,combinationsofknownmoleculesarenotpatentableunderIndianpatentlaw.174,175,176
Nevertheless,divisionalapplications(atypeofpatentapplicationwhichcontainsmatterfromapreviouslyfiledapplication)havebeenfiledbyGileadforthisandotherpatentapplications.Thismeansthatalthoughthepatentwasnotgranted,thepatentapplicationsarestillpendingbeforethepatentoffice.116,117
ThesameistrueinBrazil,whereanestimated37,000PLHAareonTDF-basedtherapies.InApril2008,thegovernmentdeclaredtenofovirasamedicineofpublicinterestforpriorityexaminationpurposes.TheNationalInstituteonIndustrialProperty(INPI–Brazilianpatentoffice)publishedthepatentrejectionforTDFon30June2009.However,Gileadhasrequestedadivisional
patent,whichhasbeenopposedbycivilsocietygroups.Inaddition,inJanuary2010,Gileadlaunchedalegalchallengeagainstthepatentoffice’sdecisiontorejectthepatent.
FollowingoppositionstothegrantofitspatentsinIndia,Gileadsignedlicensingagreementswith11genericmanufacturersinIndiaandoneinSouthAfrica,allowingthemtomanufactureandexportgenericversionsofGilead’sproductstoalimitedpre-definedlistofcountries,againstthepaymentofa5%royalty.103
ManufacturersthathavesignedtheseagreementsareunabletosupplycountriessuchasBrazilandChina,leavingthesecountriesunabletobenefitfromcompetitivepricesandimproveaccess.AfternegotiationwithGilead,BrazilistodaypayingUS$715perpatientperyearfortenofovir,overeighttimesthebestavailablegenericprice.129
Suchlicensingagreementscancontributetoincreasedcompetitionandimprovedaccesstoaffordablemedicines,butshouldalsobeofferedtomanufacturersoutsideIndia,andshouldnotincludegeographicmarketlimitations.
PaediatricsTenofovirisapprovedforadolescentsfrom12yearsold.However,nopaediatricfixed-dosecombinationhasbeendevelopedwithtenofovirandlamivudine.
ThePaediatricAntiretroviralWorkingGroupofWHOconsidersthedevelopmentofofafixed-dosecombinationofTDF/3TC75/75mgtabletandascored300/300mgtablettobeahighpriority.137
Médecins Sans Frontières | July 2010
TEN
OFO
VIR
DIS
OP
RO
xIL
FU
MA
RA
TE/LA
MIV
UD
INE/EFA
VIR
EN
Z (
TD
F/�
TC
/EFV
)FIx
ED
-DO
SE C
OM
BIN
AT
ION
S A
ND
CO
-PA
Ck
S
TENOFOVIR DISOPROxIL FUMARATE/ LAMIVUDINE/EFAVIRENZ ( TDF/�TC/EFV )
��
US$
pp
y
Month/Year
600
500
400
300
200
100
0Jun 07 Jun 08 Dec 09 Jun 10
lowest originator price
generic price
TDF/3TC/EFV 300/300/600mg tablet
505
176
513
426
GENERAL INFORMATION
•Therapeuticclass:oneNtRTI+oneNRTI+oneNNRTIinatriplefixed-dosecombination.
•Indicatedforfirst-lineforadultsandadolescents.8
•Includedin16theditionoftheWHOModelListofEssentialMedicines(EML).26
PRICE INFORMATIONDeveloping country prices in US$ per patient per year, as quoted by companies. Thepriceinbracketscorrespondstothepriceofonetabletco-pack.ProductsincludedintheWHOListofPrequalifiedMedicinalProducts(asofApril2010)areinbold.
•TheWHOExpertCommitteeontheSelectionandUseofEssentialMedicinesrecommendsandendorsestheuseoffixed-dosecombinationsandthedevelopmentofappropriatenewfixed-dosecombinations.26
•Mostpatentsrelatedtotenofovir(TDF),lamivudine(3TC)ortoefavirenz(EFV)alsoaffectthiscombination.Inaddition,otherpatentsmayhavebeenappliedformorespecificallyrelatedtotheuseofthesemedicinesincombination,ortothisspecificFDC.
Evolution of the lowest quoted price for developing countries since �00�:
AsofApril2010,therewasonegenericsourceofTDF/3TC/EFV300/300/600mgtabletincludedintheWHOListofPrequalifiedMedicinalProducts.Itspriceisshownhere.Asthereisnooriginatorfixed-dosecombinationorco-pack,thepriceshownfortheoriginatorproductisthesumofthethreeindividualoriginatorproducts.
Oververyshorttime,since2007,thegenericpricehasdroppedby59%.
(CF)TheClintonFoundationhasnegotiatedwiththismanufacturerforreducedpricesonsomeformulationsforcountriesintheirconsortium.Seeannex13fordetails.
Dailydose Cipla Matrix(CF)
Whocanaccessthisprice? Norestrictions
TDF/3TC/EFV300/300/600mgtablet
1219(0.600)
176 (0.483)
Untangling the Web of ARV Price Reductions | Please check utw.msfaccess.org
SPOTLIGHT ON ACCESS ISSUES
Thiscombinationislikelytobewidelyusedindevelopingcountriesasabackboneinfirst-andsecond-lineregimens.
InDecember2009,WHOreleasednewrecommendationsforantiretroviraltherapyfor HIVinadultsandadolescents.Thesenewrecommendationsadvisecountriestophaseoutstavudine-basedregimensbecauseoftheirlong-termirreversiblesideeffectsandtomovetowardszidovudineortenofovir-basedfirst-lineregimens.9
Formanyyears,thestavudine-containing(d4T)regimenhasplayedacrucialroleinARTscale-upinresource-limitedsettings,duetoitsavailabilityinafixed-dosecombinationandmostimportantlyitslowcost.d4Tremainsawidely-usedARVinfirst-lineregimens.
Itistime,however,forcountriestoinvestinamorerobust,TDF-basedfirst-lineregimen,suchasTDF/3TC/EFVorTDF/FTC/EFV,whichisonepillonceaday.Whilethepricetodayisstillhigherthanad4T-basedregimen,thereisaneedtogenerategreaterdemandwhichwill,inturn,increasethecompetitionneededtofurtherdecreaseprices.9
Inaddition,efavirenz(EFV)isthepreferredNNRTIforuseinpatientsstartingARTwhileonTBtreatment.
Today,thereisonegenericsourceofTDF/3TC/EFVincludedintheWHOListofPrequalifiedMedicinalProducts.
TEN
OFO
VIR
DIS
OP
RO
xIL
FU
MA
RA
TE/LA
MIV
UD
INE/EFA
VIR
EN
Z ( T
DF/�
TC
/EFV
)FIx
ED
-DO
SE C
OM
BIN
AT
ION
S A
ND
CO
-PA
Ck
S
PatentsThiscombinationisproducedbyIndiangenericcompaniesbecausenoneoftheindividualcomponentsispatentedinIndiatoday.However,GileadhasappliedforpatentsrelatedtoTDF.IfthesepatentsaregrantedinIndia,genericcompetitionforthisproductmaybeaffected.
Inamajorvictoryforaccesstomedicines,theIndianpatentofficerejectedseveralpatentapplicationsrelatingtoTDFinSeptember2009.Thepatentswererejectedonthegroundsthattheylackaninventivestep–theydonotmeettherequirementofenhancedefficacystipulatedunderSection3(d)ofIndia’spatentlaw.Further,combinationsofknownmoleculesarenotpatentableunderIndianpatentlaw.174,175,176
Nevertheless,divisionalapplications(atypeofpatentapplicationwhichcontainsmatterfromapreviouslyfiledapplication)havebeenfiledbyGileadforthisandotherpatentapplications.Thismeansthatalthoughthepatentwasnotgranted,thepatentapplicationsarestillpendingbeforethepatentoffice.116,117
ThesameistrueinBrazil,whereanestimated37,000PLHAareonTDF-basedtherapies.InApril2008,thegovernmentdeclaredtenofovirasamedicineofpublicinterestforpriorityexaminationpurposes.TheNationalInstituteonIndustrialProperty(INPI)publishedthepatentrejectionforTDFon
30June2009.However,Gileadhasalsorequestedadivisionalpatentforthepreviouslyrejectedpatent.
FollowingoppositionstothegrantofitspatentsinIndia,Gileadsignedlicensingagreementswith11genericmanufacturersinIndiaandoneinSouthAfrica,allowingthemtomanufactureandexportgenericversionsofGilead’sproductstoalimitedpre-definedlistofcountries,againstthepaymentofa5%royalty.103
ManufacturersthathavesignedtheseagreementsareunabletosupplycountriessuchasBrazilandChina,leavingthesecountriesunabletobenefitfromcompetitivepricesandimproveaccess.AfternegotiationwithGilead,BrazilistodaypayingUS$715perpatientperyearfortenofovir,overeighttimesthebestavailablegenericprice.129
Suchlicensingagreementscancontributetoincreasedcompetitionandimprovedaccesstoaffordablemedicines,butshouldalsobeofferedtomanufacturersoutsideIndia,andshouldnotincludegeographicmarketlimitations.
PaediatricsTenofovirisapprovedforadolescentfrom12yearsold.However,nopaediatricfixed-dosecombinationhasbeendevelopedwithtenofovir,lamivudineandefavirenz.
��
Médecins Sans Frontières | July 2010
ZIDOVUDINE/ LAMIVUDINE ( AZT/�TC )
Oct 01
Dec 02
Jun02
Dec03
May03
Feb05
Apr04
Jun06
Jun05
Jun 07
Jun 08
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Jun10
US$
pp
y
Month/Year
800
700
600
500
400
300
200
100
0
lowest originator price
generic price
AZT/3TC 300/150mg tablet
197
730
270
110
�0
ZID
OV
UD
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/ L
AM
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AZ
T/ �
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)F
IxE
D-D
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CO
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Ck
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Evolution of the lowest price quoted for developing countries since �00�:
AsofApril2010,therewereninegenericsourcesofAZT/3TC300/150mgtabletincludedintheWHOListofPrequalifiedMedicinalProducts.Theonewiththelowestpriceisshownhere.
CompetitionamongWHOprequalifiedsourcescontinues,andhasledtoasteadydecreaseinpricesoftheoriginatorproductby73%andthegenericby59%since2001.
GENERAL INFORMATIONGENERAL INFORMATION
•Therapeuticclass:twoNRTIsindoublefixed-dosecombination.
•Indicatedforfirst-andsecond-lineforadults,adolescentsandchildren.8,137
•Originatorcompanyandproductbrandname:GlaxoSmithKline(GSK),Combivir.InApril2009,PfizerandGSKjointlyannouncedthecreationofViiV,anewjointventurefocusingsolelyontheR&DandcommercialisationofHIVmedicines.
•FirstapprovalbyU.S.FoodandDrugAdministration(FDA):September1997.17
•Includedinthe16theditionoftheWHOModelListofEssentialMedicines(EML).26
•TheWHOExpertCommitteeontheSelectionandUseofEssentialMedicinesrecommendsandendorsestheuseoffixed-dosecombinationsandthedevelopmentofappropriatenewfixed-dosecombinations.26
•Worldsalesoftheoriginator:2009:US$649million;2008:$713million;2007:$888million;2006:$1billion;2005:$1.1billion;2004:$1.1billion.77,78,79,80,81,82
•Mostpatentsrelatedtozidovudine(AZT)ortolamivudine(3TC)alsoaffectthiscombination.Inaddition,GSKappliedforpatentsspecificallyrelatedtotheuseofAZTand3TCincombination,178andforthetabletformulationoftheFDC,179whichareduetoexpirein2012and2017,respectively.
Dailydose
ViiV Aurobindo(CF) Cipla(CF) Hetero(CF) Matrix(CF) Ranbaxy Strides
Whocanaccessthisprice?
Seeannex2 Norestrictions
AZT/3TC60/30mgtablet
4 95 (0.065)
121 (0.083)
88(0.060)
AZT/3TC300/150mgtablet
2 197 (0.270)
112 (0.154)
111 (0.152)
115 (0.158)
110 (0.150)
110 (0.150)
131 (0.180)
(CF)TheClintonFoundationhasnegotiatedwiththismanufacturerforreducedpricesonsomeformulationsforcountriesintheirconsortium.SeeAnnex13fordetails.
PRICE INFORMATIONDeveloping country prices in US$ per patient per year, as quoted by companies. Thepriceinbracketscorrespondstothepriceofonetablet.ProductsincludedintheWHOListofPrequalifiedMedicinalProducts(asofApril2010)areinbold.
Untangling the Web of ARV Price Reductions | Please check utw.msfaccess.org
ZID
OV
UD
INE
/ L
AM
IVU
DIN
E ( A
ZT
/ �
TC
)F
IxE
D-D
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CO
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ND
CO
-PA
Ck
S
SPOTLIGHT ON ACCESS ISSUES
Formanyyears,thestavudine-containing(d4T)regimenhasplayedacrucialroleinARTscale-upinresource-limitedsettings,duetoitsavailabilityinafixed-dosecombinationand,mostimportantly,itslowcost.d4Tremainsawidely-usedARVinfirst-lineregimens.
InDecember2009,WHOreleasednewrecommendationsforantiretroviraltherapyforHIVinadultsandadolescents.Thesenewrecommendationsadvisecountriestophaseoutstavudine-basedregimensbecauseoftheirlong-termirreversiblesideeffectsandtomovetowardszidovudineortenofovir-basedfirst-lineregimens.9
Forsecond-linetreatment,AZTincombinationwithlamivudine(3TC)orFTCistherecommendedNRTIbackbone,tobeaddedtoaboostedproteaseinhibitor,iftenofovirhasbeenusedinthefirst-lineregimen.
PatentsGenericversionsofthiscombinationweredevelopedincountrieswhereneitherofthemolecules,northeircombination,
werepatented.However,thegenericversionsofthemedicineproducedinIndiacameunderthreatwhenIndiabegangrantingpatentsonpharmaceuticalsin2005,asGlaxoSmithKline(GSK)hadappliedforapatentonthecombination.
CivilsocietyorganisationsinIndiaopposedthepatentapplicationinMarch2006,127whichresultedinGSKcommunicatinginAugust2006thatpatentsspecificallyrelatedtothefixed-dosecombinationwerebeingwithdrawninallcountries.180
Yetinsomecountries,genericversionsoftheFDCarenotavailablebecauseofGSKpatentrights.InChina,forexample,GSK’sexclusiverightson3TCalonehaveledtothefactthatonlytheoriginatorproductisavailableatUS$1,839perpatientperyear.
PaediatricsThemostcommonlyusedfirst-lineregimensforchildrentodayareeitherAZT+3TC+NVPord4T+3TC+NVP.Withbothoftheseregimens,thereisaneedtostart
theNVPatalowerdoseforthefirsttwoweekstominimisethesideeffects.
Quality-assureddoublefixed-dosecombinationsarethereforeofgreatvalueinallowingchildrentobesafelyandaccuratelydosedwhilestartingtreatment.Intheirabsence,thealternativeistousetwodifferentsyrups,whichcanbedifficulttoadminister.Today,therearetwopaediatricAZT/3TCfixed-dosecombinationtabletsincludedintheWHOListofPrequalifiedMedicinalProducts.
��
Médecins Sans Frontières | July 2010
ZID
OV
UD
INE
/L
AM
IVU
DIN
E/A
BA
CA
VIR
( A
ZT
/�
TC
/A
BC
)F
IxE
D-D
OSE
CO
MB
INA
TIO
NS A
ND
CO
-PA
Ck
S
ZIDOVUDINE/LAMIVUDINE/ABACAVIR ( AZT/�TC/ABC )
��
GENERAL INFORMATION
•Therapeuticclass:threeNRTIsintriplefixed-dosecombination.
•Indicatedunderspecificconditionsinadults,adolescentsandchildren.8,137
•TheWHOExpertCommitteeontheSelectionandUseofEssentialMedicinesrecommendsandendorsestheuseoffixed-dosecombinationsandthedevelopmentofappropriatenewfixed-dosecombinations.26
•Originatorcompanyandproductbrandname:GlaxoSmithKline(GSK),Trizivir.InApril2009,PfizerandGSKjointlyannouncedthecreationofViiV,anewjointventurefocusingsolelyontheR&DandcommercialisationofHIVmedicines.
•FirstapprovalbyU.S.FoodandDrugAdministration(FDA):November2000.17
•Worldsalesoforiginatorproduct:2009:US$307million;2008:$350million;2007:$455million;2006:$529million;2005:$598million;2004:$635million.77,78,79,80,81,82
•Mostpatentsonzidovudine(AZT),lamivudine(3TC),AZT/3TCorabacavir(ABC)alsoaffectthiscombination.Inaddition,GSKappliedforpatentsmorespecificallyrelatedtothetriplecombination.173
PRICE INFORMATIONDeveloping country prices in US$ per patient per year, as quoted by companies. Thepriceinbracketscorrespondstothepriceofonetablet.ProductsincludedintheWHOListofPrequalifiedMedicinalProducts(asofApril2010)areinbold.
Dailydose
ViiV Cipla Matrix Ranbaxy
Whocanaccessthisprice? Seeannex2
AZT/3TC/ABC60/30/60mgtablet
4244 (0.167)
AZT/3TC/ABC300/150/300mgtablet
2653 (0.895)
414(0.567)
365(0.500)
548 (0.750)
Oct 01
Dec 02
Jun02
Dec03
May03
Feb05
Apr04
Jun06
Jun05
Jun 07
Jun 08
Dec09
Jun10
US$
pp
y
Month/Year
3000
2500
2000
1500
1000
500
0
lowest originator price
generic price
AZT/3TC/ABC 300/150/300mg tablet
653
548
1648
2409
Evolution of the lowest price quoted for developing countries since �00�:
AsofApril2010,therewasonegenericsourceofAZT/3TC/ABC300/150/300mgtabletincludedintheWHOListofPrequalifiedMedicinalProducts.Itspriceisshownhere.
Therehasbeenadecreaseof67%inthegenericpriceand73%intheoriginatorpricesince2001.
Untangling the Web of ARV Price Reductions | Please check utw.msfaccess.org ��
ZID
OV
UD
INE
/L
AM
IVU
DIN
E/A
BA
CA
VIR
( AZ
T/�
TC
/A
BC
)F
IxE
D-D
OSE
CO
MB
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NS A
ND
CO
-PA
Ck
S
SPOTLIGHT ON ACCESS ISSUES
ThisFDCistheonlytripleNRTIformulationavailable.
Thiscombinationisnolongerapreferredregimeninthedevelopedworld.181
Inthedevelopingworld,itsuseislimitedtoindividualswithcontra-indicationtoNNRTI-basedregimensorwhoareunabletotoleratethem.Thisappliesparticularlyforpeopleco-infectedwithTB/HIV,pregnantwomen,patientswithchronicviralHepatitisandthosewithHIV-2infection.137
PatentsGlaxoSmithKline(GSK)couldnotapplyforbasicpatentsrelatedto
abacavir(ABC),zidovudine(AZT)orlamivudine(3TC)insomedevelopingcountriessuchasIndia,whichdidnotgrantpatentsonpharmaceuticalsatthetime.ThisallowedIndiangenericcompaniestodevelopgenericversionsofeachmedicine,andofthecombination.
However,GSKwidelyappliedforpatentsinotherdevelopingcountries,wherepossible.
InIndia,GSKhadappliedforpatentsmorespecificallyrelatedtothefixed-dosecombination.Thecompanywithdrewthepatentapplicationafterapre-grantoppositionwasfiledin2006.182
PaediatricsThepaediatricformulationofAZT/3TC/ABCisagenericversionandisnowincludedintheWHOListofPrequalifiedMedicinalProducts.
However,thisproductisnotcommerciallyavailableyetbecausethereisnotenoughmarketdemandtomaketheproductcommerciallyviable.
Médecins Sans Frontières | July 2010
ZID
OV
UD
INE
/ L
AM
IVU
DIN
E/ N
EV
IRA
PIN
E (
AZ
T/ �
TC
/ N
VP
)F
IxE
D-D
OSE
CO
MB
INA
TIO
NS A
ND
CO
-PA
Ck
S
ZIDOVUDINE/LAMIVUDINE/NEVIRAPINE ( AZT/�TC/NVP )
GENERAL INFORMATION
•Therapeuticclass:twoNRTI+oneNNRTIintriplefixed-dosecombination.
•Indicatedforfirst-lineforadults,adolescentsandchildren.8,137
•Includedinthe16theditionoftheWHOModelListofEssentialMedicines(EML).26
•TheWHOExpertCommitteeontheSelectionandUseofEssentialMedicinesrecommendsandendorsestheuseoffixed-dosecombinationsandthedevelopmentofappropriatenewfixed-dosecombinations.26
•Mostpatentsrelatedtozidovudine(AZT),lamivudine(3TC),AZT/3TCortonevirapine(NVP)alsoaffectthiscombination.Inaddition,otherpatentsmayhavebeenappliedformorespecificallyrelatedtotheuseofthesemedicinesincombination,orforthisspecificFDC.
��
Dailydose
Aurobindo(CF) Cipla(CF) Hetero(CF) Matrix(CF) Ranbaxy Strides
Whocanaccessthisprice? Norestrictions
AZT/3TC/NVP60/30/50mgdispersibletablet
4 158 (0.108)
183(0.125)
AZT/3TC/NVP300/150/200mgtablet
2 148 (0.203)
137 (0.188)
155 (0.213)
143 (0.196)
145 (0.199)
139(0.190)
PRICE INFORMATIONDeveloping country prices in US$ per patient per year, as quoted by companies. Thepriceinbracketscorrespondstothepriceofonetablet.ProductsincludedintheWHOListofPrequalifiedMedicinalProducts(asofApril2010)areinbold.
(CF)TheClintonFoundationhasnegotiatedwiththismanufacturerforreducedpricesonsomeformulationsforcountriesintheirconsortium.Seeannex13fordetails.
Oct 01
Dec 02
Jun02
Dec03
May03
Feb05
Apr04
Jun06
Jun05
Jun 07
Jun 08
Dec09
Jun10
US$
pp
y
Month/Year
1600
1400
1200
1000
800
600
400
200
0
lowest originator price
generic price
AZT/3TC/NVP 300/150/200mg tablet
137
419 441
1356
Evolution of the lowest price quoted for developing countries since �00�:
AsofApril2010,thereweresixgenericsourcesofAZT/3TC/NVP300/150/200mgtabletincludedintheWHOListofPrequalifiedMedicinalProducts.Theonewiththelowestpriceisshownhere.Asthereisnooriginatorfixed-dosecombinationorco-pack,thepriceshownfortheoriginatorproductisthesumofthethreeindividualoriginatorproducts.
Genericpriceshavesteadilydecreasedby67%since2002.
Untangling the Web of ARV Price Reductions | Please check utw.msfaccess.org
ZID
OV
UD
INE
/ L
AM
IVU
DIN
E/ N
EV
IRA
PIN
E ( A
ZT
/ �
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/ N
VP
)F
IxE
D-D
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CO
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INA
TIO
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ND
CO
-PA
Ck
S
SPOTLIGHT ON ACCESS ISSUES
Formanyyears,thestavudine-
containing(d4T)regimenhas
playedacrucialroleinARTscale-up
inresource-limitedsettings,due
toitsavailabilityinafixed-dose
combinationand,mostimportantly,
itslowcost.d4Tremainsawidely-
usedARVinfirst-lineregimens.
InDecember2009,WHOreleased
newrecommendationsfor
antiretroviraltherapyforHIVin
adultsandadolescents.Thesenew
recommendationsadvisecountries
tophaseoutstavudine-based
regimensbecauseoftheirlongterm
irreversiblesideeffectsandtomove
towardszidovudineortenofovir-
basedfirst-lineregimens.9
PatentsInadditiontothegenericmanufacturersreferencedabove,ApotexalsomanufacturesanAZT/3TC/NVPfixed-dosecombination183forexporttodevelopingcountriesunderthe30August2003WorldTradeOrganizationdecisiononcompulsorylicensingforexport.184
Inearly2004,MSFmadetheoriginalrequestforthedevelopmentofthisFDCtoApotex,asnogenericversionsoftheFDCwereavailableatthetime.185
MSF,however,ultimatelyendedupprocuringtheFDCfrommanufacturersinIndia,whichreachedthemarketearlierbecausetheIndianmanufacturerswerenothamperedbytheproceduralrequirementsofthenewWTOrulesonCLforexport.
PaediatricsThemost-commonlyusedfirst-lineregimensforchildrentodayareeitherAZT+3TC+NVPord4T+3TC+NVP.
TodaythereisonlyonegenericpaediatricAZT/3TC/NVPfixed-dosecombinationincludedintheWHOListofPrequalifiedMedicinalProducts.
��
Médecins Sans Frontières | July 2010
ZID
OV
UD
INE
/L
AM
IVU
DIN
E +
EFA
VIR
EN
Z (
AZ
T/�
TC
+ E
FV
)F
IxE
D-D
OSE
CO
MB
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TIO
NS A
ND
CO
-PA
Ck
S
ZIDOVUDINE/LAMIVUDINE + EFAVIRENZ ( AZT/�TC + EFV )
��
Formanyyears,thed4T-containingregimenhasplayedacrucialroleinARTscale-upinresource-limitedsettings,duetoitsavailabilityinafixed-dosecombinationandmostimportantlyitslowcost.d4Tremainsawidely-usedARVinfirst-lineregimens.
InDecember2009,WHOreleasednewrecommendationsforantiretroviraltherapyforHIVinadultsandadolescents.Thesenewrecommendationsadvisecountries
SPOTLIGHT ON ACCESS ISSUES
tophaseoutstavudine-basedregimensbecauseoftheirlongtermirreversiblesideeffectsandtomovetowardszidovudineortenofovir-basedfirst-lineregimens.
Inaddition,efavirenz(EFV)isthepreferredNNRTIforuseinpatientsstartingARTwhileonTBtreatment.9
PatentsBasicpatentsrelatedtozidovudine(AZT),lamivudine(3TC)orefavirenz(EFV)couldnotbeobtainedinsome
developingcountriessuchasIndia,whichdidnotgrantproductpatentsonpharmaceuticalsatthetime.
ThisallowedIndiandrugcompaniestomanufacturegenericversionsofthemedicinesandtodevelopthisproduct.
However,GlaxoSmithKlineandMerckmayholdpatentsinotherdevelopingcountries,whichcouldpreventtheimportationanduseofthisfixed-dosecombination.
US$
pp
y
Month/Year
600
500
400
300
200
100
0Jun 06 Jun 07 Jun 08 Dec 09 Jun 10
lowest originator price
generic price
AZT/3TC + EFV 300/150 + 600mg tablets (co-pack)
189
462451
558
GENERAL INFORMATION
•Therapeuticclass:twoNRTI+oneNNRTIinaco-pack.
•Indicatedforfirst-lineforadults,adolescentsandchildren.8,137
•TheWHOExpertCommitteeontheSelectionandUseofEssentialMedicinesrecommendsandendorsestheuseoffixed-dosecombinationsandthedevelopmentofappropriatenewfixed-dosecombinations.26
•Mostpatentsrelatedtozidovudine(AZT),lamivudine(3TC),AZT/3TCortoefavirenz(EFV)alsoaffectthiscombination.Inaddition,CiplaappliedforpatentsspecificallyrelatedtotheuseofAZT,3TCandEFVincombination.186
Evolution of the lowest quoted price for developing countries since �00�:
AsofApril2010,therewerethreegenericsourcesofAZT/3TC+EFV300/150+600mgtablets(co-pack)includedintheWHOListofPrequalifiedMedicinalProducts.Theonewiththelowestpriceisshownhere.Asthereisnooriginatorco-pack,thepriceshownfortheoriginatorproductisthesumofthetwoindividualoriginatorproducts.
Since2006,thepriceofgenerichasdroppedby58%.
PRICE INFORMATIONDeveloping country prices in US$ per patient per year, as quoted by companies. Thepriceinbracketscorrespondstothepriceofonekit(3tablets).ProductsincludedintheWHOListofPrequalifiedMedicinalProducts(asofApril2010)areinbold.
Dailydose Aurobindo Cipla Ranbaxy Strides
Whocanaccessthisprice? Norestrictions
AZT/3TC+EFV300/150+600mgtablets(co-pack)
1kit(3tablets)
231 (0.633)
320(0.877)
322 (0.883)
189 (0.517)
Untangling the Web of ARV Price Reductions | Please check utw.msfaccess.org ��
AN
NE
x �
: SU
MM
AR
y O
F P
RIC
ES IN
US$
qU
OT
ED
By
CO
MPA
NIE
S F
OR
EL
IGIB
LE
DE
VE
LO
PIN
G C
OU
NT
RIE
S
ANNEx �: SUMMARy TABLE - ALL PRICES ON ONE PAGE
Developing country prices in US$ per patient per year, as quoted by companies. Thepriceinbracketscorrespondstothepriceofoneunit(tablet,capsule,etc.).ProductsincludedintheWHOListofPrequalifiedMedicinalProducts(asofApril2010)areinbold.
ARVs in alphabetical order
Daily dose Originator company Generic companies
Abacavir (ABC) ViiV Aurobindo Cipla Hetero Matrix Ranbaxy Strides
20mg/mloralsolution 10ml 230 (0.063/ml)
212 (0.058/ml)
113 (0.031/ml)
60mgtablet 4 153 (0.105)
134(0.092)
183 (0.125)
540(0.370)
300mgtablet 2 438 (0.600)
243 (0.333)
207 (0.283)
256(0.350)
219 (0.300)
274 (0.375)
Atazanavir (ATV)*BMS
MatrixCategory1countries
Category2countries
150mgcapsule 2 353 (0.484)
431 (0.590)
200mgcapsule xx (0.602) (0.743)
300mgcapsule 1 256(0.700)
Darunavir (DRV)* Tibotec
300mgtablet 4 1095(0.750)
Didanosine (ddI)BMS
Aurobindo Cipla RanbaxyCategory1countries
Category2countries
2gpowderforreconstitution(finalconcentration10mg/ml)
12ml 276 (12.590/2g)
308 (14.057/2g)
88 (4.000/2g)
25mgtablet 5 212 (0.116)
429 (0.235)
115(0.063)
228(0.125)
50mgtablet xx (0.158) (0.235) (0.079) (0.115)
100mgtablet 4 311 (0.213)
364 (0.249)
194 (0.133)
188(0.129)
242(0.166)
125mgenteric-coatedcapsule 1 110
(0.300)
150mgtablet xx (0.308) (0.345) (0.225) (0.167)
200mgtablet xx (0.267) (0.257)
200mgenteric-coatedcapsule xx (0.383)
250mgenteric-coatedcapsule 1 223
(0.611)249 (0.683)
170 (0.467)
103(0.283)
400mgenteric-coatedcapsule 1 288
(0.789)322 (0.881)
256 (0.700)
132(0.363)
Efavirenz (EFV)Merck
Aurobindo Cipla Hetero Matrix Ranbaxy StridesCategory1countries
Category2countries
30mg/mlsuspension xx (0.094/ml) (0.151/ml)
50mgcapsule xx (0.083)
50mgtablet xx (0.120) (0.210) (0.083)
100mgcapsule xx (0.150)
200mgcapsule 3 130 (0.119)
134 (0.122)
152(0.139)
118 (0.108)
200mgtablet 3 394 (0.360)
821 (0.750)
146 (0.133)
110 (0.100)
600mgtablet 1 237 (0.650)
657 (1.800)
73 (0.200)
79 (0.217)
82 (0.225)
61 (0.167)
91 (0.250)
62 (0.170)
*TherequiredadditionofRTVasaboostermustalsobeconsideredinthefinalcostofthisdrug.
Médecins Sans Frontières | July 2010��
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Daily dose Originator company Generic companies
Emtricitabine (FTC) Aurobindo Matrix
200mgcapsule 163 (0.173)
79 (0.217)
Etravirine (ETV) Tibotec
100mgtablet 4913(0.625)
Fosamprenavir (FPV)* ViiV
50mg/mlsuspension 12ml648(0.148/ml)
700mgtablet 21222(1.674)
Indinavir (IDV)*
Merck
Aurobindo Cipla HeteroCategory1countries
Category2countries
400mgcapsule 4394 (0.270)
686 (0.470)
292(0.200)
422(0.289)
390 (0.267)
Lamivudine (3TC) ViiV Aurobindo Cipla Hetero Matrix Ranbaxy Strides
10mg/mloralsolution
10ml84 (0.023/ml)
29 (0.008/ml)
37 (0.010/ml)
37(0.010/ml)
150mgtablet 264 (0.087)
34 (0.047)
35 (0.048)
33 (0.045)
34 (0.046)
34 (0.047)
37 (0.050)
300mgtablet 124 (0.067)
41(0.113)
38 (0.103)
34 (0.092)
Lopinavir/ ritonavir (LPV/r)
Abbott
Aurobindo Cipla Hetero MatrixCategory1countries
Category2countries
80/20mg/mloralsolution
4ml176 (0.121/ml)
400 (0.274/ml)
100/25mgheat-stabletablet
3165 (0.151)
376 (0.343)
219 (0.200)
228 (0.208)
133/33mgsoft-gelcapsule
6500 (0.228)
1000 (0.457)
609(0.278)
200/50mgheat-stabletablet
4440 (0.301)
1000 (0.685)
475 (0.325)
463(0.317)
493(0.338)
486 (0.333)
Nelfinavir (NFV)
Roche
CiplaCategory1countries
Category2countries
50mg/goralpowder 24g2129 (0.243/g)
2462 (0.281/g)
250mgtablet 101566 (0.429)
2427 (0.665)
945(0.259)
Nevirapine (NVP)
Boehringer
Aurobindo Cipla Hetero Huahai Matrix Ranbaxy StridesCategory1countries
Category2countries
10mg/mlsuspension 20ml380 (0.052/ml)
533 (0.073/ml)
66 (0.009/ml)
73 (0.010/ml)
200mgtablet 2219 (0.300)
438 (0.600)
39 (0.054)
34 (0.046)
37 (0.050)
34 (0.047)
39 (0.054)
39 (0.053)
37 (0.050)
Raltegravir (RAL)
Merck
Category1countries
400mgtablet 21113(1.525)
*TherequiredadditionofRTVasaboostermustalsobeconsideredinthefinalcostofthisdrug.
Untangling the Web of ARV Price Reductions | Please check utw.msfaccess.org ��
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Daily dose Originator company Generic companies
Ritonavir (RTV)Abbott
CiplaCategory1countries
80mg/mloralsolution xx (0.093/ml)
100mgsoft-gelcapsule 2 83 (0.114)
323(0.442)
100mgheat-stabletablet 2 83(0.114)
Saquinavir (SQV)*Roche
CiplaCategory1countries
Category2countries
200mghardcapsule 10 1212 (0.332)
2427 (0.665)
1621(0.444)
500mgtablet 4 1113 (0.762)
2427 (1.662)
Stavudine (d4T)BMS
Aurobindo Cipla Hetero Matrix Ranbaxy StridesCategory1countries
Category2countries
1mg/mlpowderfororalsolution 20ml 51
(0.007/ml)58 (0.008/ml)
58 (0.008/ml)
44 (0.006/ml)
15mgcapsule xx (0.082) (0.093) (0.026) (0.024) (0.025)
20mgcapsule xx (0.089) (0.093) (0.027) (0.025) (0.028)
30mgcapsule 2 48 (0.066)
68 (0.093)
20 (0.028)
26(0.035)
21 (0.029)
24 (0.033)
26 (0.035)
22 (0.030)
Tenofovir (TDF)Gilead
Aurobindo Cipla Hetero Matrix Ranbaxy StridesCategory1countries
Category2countries
300mgtablet 1 204 (0.559)
360 (0.986)
100 (0.275)
87 (0.237)
103(0.283)
85 (0.233)
152 (0.417)
146(0.400)
Zidovudine (AZT) ViiV Aurobindo Cipla Hetero Matrix Ranbaxy
10mg/mloralsolution 20ml 234 (0.032/ml)
66 (0.009/ml)
80 (0.011/ml)
66(0.009/ml)
60mgtablet 4 115 (0.079)
100mgcapsule xx (0.122) (0.051) (0.050)
250mgcapsule xx (0.276)
300mgtablet 2 161 (0.221)
101 (0.138)
97 (0.133)
100 (0.137)
91 (0.125)
91 (0.125)
ABC/3TC ViiV Aurobindo Cipla Matrix
60/30mgtablet 4 175 (0.120)
244 (0.167)
600/300mgtablet 1 484(1.326)
134 (0.367)
152(0.417)
3TC/d4T Aurobindo Cipla Hetero Matrix Ranbaxy Strides
30/6mgdispersibletablet 4 47 (0.032)
60/12mgdispersibletablet 2 40
(0.055)
150/30mgtablet 2 50 (0.068)
42 (0.057)
51(0.070)
42 (0.058)
42 (0.058)
44 (0.060)
3TC/d4T/NVP Aurobindo Cipla Hetero Matrix Ranbaxy Strides
30/6/50mgdispersibletablet 4 55
(0.038)
60/12/100mgdispersibletablet 2 53
(0.072)
150/30/200mgtablet 2 67 (0.092)
67 (0.092)
73 (0.100)
67 (0.092)
70 (0.096)
73 (0.100)
*TherequiredadditionofRTVasaboostermustalsobeconsideredinthefinalcostofthisdrug.
Médecins Sans Frontières | July 2010�0
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Daily dose Originator company Generic companies
3TC/d4T + EFV Cipla Ranbaxy Strides
150/30+600mgtablets(co-pack)
1kit(3tabs)
274(0.751)
304 (0.833)
106(0.290)
TDF/FTC
Gilead
Aurobindo Cipla Hetero MatrixCategory1countries
Category2countries
300/200mgtablet 1315 (0.863)
540 (1.479)
155 (0.425)
158(0.433)
164(0.450)
143 (0.392)
TDF/FTC/EFV
BMS/Gilead/Merck
Cipla MatrixCategory1countries
Category2countries
300/200/600mgtablet 1613 (1.680)
1033 (2.830)
268(0.733)
219 (0.600)
TDF/3TC Cipla Hetero Matrix
300/300mgtablet 1122(0.333)
128 (0.350)
107 (0.294)
TDF/3TC/EFV Cipla Matrix
300/300/600mgtablet 1219(0.600)
176 (0.483)
AZT/3TC ViiV Aurobindo Cipla Hetero Matrix Ranbaxy Strides
60/30mgtablet 495 (0.065)
121 (0.083)
88(0.060)
300/150mgtablet 2197 (0.270)
112 (0.154)
111 (0.152)
115 (0.158)
110 (0.150)
110 (0.150)
131 (0.180)
AZT/3TC/ABC ViiV Cipla Matrix Ranbaxy
60/30/60mgtablet
4244 (0.167)
300/150/300mgtablet 2653 (0.895)
414(0.567)
365(0.500)
548 (0.750)
AZT/3TC/NVP Aurobindo Cipla Hetero Matrix Ranbaxy Strides
60/30/50mgdispersibletablet
4158 (0.108)
183(0.125)
300/150/200mgdispersibletablet
2148 (0.203)
137 (0.188)
155 (0.213)
143 (0.196)
145 (0.199)
139(0.190)
AZT/3TC + EFV Aurobindo Cipla Ranbaxy Strides
300/150+600mgtablets(co-pack)
1kit(3tabs)
231 (0.633)
320(0.877)
322 (0.883)
189 (0.517)
Untangling the Web of ARV Price Reductions | Please check utw.msfaccess.org ��
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ANNEx �: CONDITIONS OF OFFER By COMPANy
Company Eligibility(countries) Eligibility(bodies) Additionalcomments Deliveryofgoods
Abbott Category1countries:AllAfricancountriesandallUnitedNationsdefinedLeast-DevelopedCountriesoutsideAfrica.
Category2countries:SeeAnnex8formoredetails.
Governmentsandprogrammesfullyfundedbygovernments,UNsystemsorganisations,NGOsandothernot-for-profitinstitutionalprovidersinlow-andlowermiddle-incomecountries.
FOB
Aurobindo Noreportedrestrictions. NGOsandgovernmentalorganisations.
Pricesavailableforabove500,000unitsfortabletpacksandabove10,000unitsfororalsolutions.
Deliveryofgoodsfourtosixweeksfromthedateofconfirmedorders.
Paymentbyletterofcredit.
FOBHyderabad(India).
BoehringerIngelheim(BI)
Category1countries:AllLDCs,alllow-incomecountriesandallofAfrica
Category2countries:Allmiddle-incomecountriesnotcoveredundercategory1.
Governments,NGOsandotherpartnerswhocanguaranteethattheprogrammeisruninaresponsiblemanner.
CIF
Bristol-MyersSquibb(BMS)
Category1countries:Sub-SaharanAfricancountries(exceptsouthernAfricancountries)pluscountriesclassifiedaslow-incomebytheWorldBank(exceptKorea,Kyrgyzstan,MoldovaandUzbekistan).
Category2countries:SouthernAfricancountries.Seeannex7formoredetails.
Forotherdevelopingcountries,pricesarenegotiatedonacase-by-casebasiswithBMSlocalrepresentatives.
Bothprivateandpublicsectororganisationsthatareabletoprovideeffective,sustainableandmedically-soundcareandtreatmentofHIV/AIDS.
Category1countriesareinvoicedinUS$.
Category2countriesareinvoicedinSouthAfricanRand.
CIPincoterm.
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Cipla Noreportedrestrictionsbuthigherpriceshavebeennegotiatedseparatelyfor10LatinAmericancountries.
Norestrictions. Noquantity-relatedconditions.Pricesforlargerquantitiesarenegotiable.
FOBMumbai(India)orCIF.
Theactualfreightischargedseparately.
Gilead Thereareover130eligiblecountries,includingallAfricanstatesandadditionalcountriesclassifiedaslow-orlowermiddle-incomebasedonacountry’seconomicstatusmeasurebygrossnationalincome(GNI)andHIVprevalence.SeeAnnex9formoredetails.
Forothercountries,pricesarenegotiatedonacase-by-casebasis.
OrganisationsthatprovideHIVtreatmentin130countriesarecoveredbytheGileadAccessProgram.
TheProgramismanagedthroughGilead’sInternationalAccessOperationsandGilead’slocaldistributionpartners.
Pleasenotethatlocaltaxes,tariffs,andlimiteddistributormark-upsmaybeaddedtotheex-factoryprices.
Shippingtermsvarybylocaldistributor.
Hetero Noreportedrestrictions. Privatesector,publicsectorandNGOs.
Pricesmaybenegotiatedonindividualbasisaccordingtocommercialterms.
FOBMumbai(India).
Huahai Noreportedrestrictions. Governments,non-profitinstitutionalprovidersofHIVcare,NGOs,andotherprivateandpublicorganisationsthatareabletoprovideresponsible,sustainableandmedicallysoundcare.
Forfinalpurchase,pricewillbefurthernegotiated,consideringthefactorslikechangesinexchangerate.
FCAShanghai.
Matrix NoreportedrestrictionsexceptCuba,Iran,NorthKorea,Syria,Sudan,Belarus,Myanmar,DRCongoandLiberia,forwhichpriorapprovalfromMylanLabsIncisrequired.
Norestrictions. Minimumorder–Onefullshipper/cartonpacks.
Ex-worksNashik,Indiaorasspecifiedbycustomers.
Merck PleaserefertoAnnex10fortheindividualdrugcountryeligibility.
Governments,internationalorganisations,NGOs,privatesectororganisations(e.g.employers,hospitalsandinsurers).
MerckmayundercertaincircumstancessupplyARVstopatientsthroughretailpharmacies.
CIP
Ranbaxy Noreportedrestrictions,buthigherpriceswerenegotiatedseparatelyfor10LatinAmericancountries.
NGOsandgovernmentsorprogrammessupportedbythem.
Confirmedletterofcreditoradvancepaymentpreferredfornewcustomers.
FOBDelhi(India).
Untangling the Web of ARV Price Reductions | Please check utw.msfaccess.org ��
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Roche Category1countries:Allcountriesinsub-SaharanAfricaandallcountriesclassifiedasLeast-DevelopedCountriesbytheUnitedNations.
Category2countries:Low-incomecountriesandlowermiddle-incomecountries,asclassifiedbytheWorldBank.
Governments,non-profitinstitutionalprovidersofHIVcare,NGOs.
CAD(CashAgainstDocuments)30daysatsight.MinimumorderanddeliveryamountpershipmentisCHF10,000.
FCABaselairport(Switzerland)orCIPairportofdestination.
StridesArcolab
Noreportedrestrictions. Governments,non-profitinstitutionalprovidersofHIVtreatment,NGOs.
Paymentbysignedletterofcredit.
FOBBangalore(India).
Tibotec Sub-SaharanAfricaandLeast-DevelopedCountries(LDCs).
Norestrictions. QuestionsregardingpricesappliedintherelatedcountriesneedtobeaddressedtoAspen.
FOB
ViiV
InApril2009,PfizerandGSKjointlyannouncedthecreationofViiV,anewjointventurefocusingsolelyontheR&DandcommercialisationofHIVmedicines.
Least-DevelopedCountries(LDCs)plussub-SaharanAfrica.
AllCountryCoordinationMechanisms(CCM)projectsfullyfinancedbytheGlobalFundtoFightAIDS,TBandMalaria,aswellasprojectsfundedbyPEPFAR.
Forotherlow-andmiddle-incomecountries,publicsectorpricesarenegotiatedonacase-by-casebasis,eitherbilaterallyorthroughtheAcceleratingAccessInitiative.
Governments,aidorganisations,charities,UNagencies,othernot-for-profitorganisationsandinternationalprocurementagencies.
Insub-SaharanAfrica,employersofferingHIV/AIDScareandtreatmentdirectlytotheiruninsuredstaffthroughworkplaceclinicsorsimilararrangements.
SupplyAgreementrequired(forNGOsrequiringfewerthan10patientpackspermonth,thisrequirementmaybewaived).
Allorganisationsmustsupplythepreferentiallypricedproductsonanot-for-profitbasis.
CIP
NOTES:
Theconditionsdetailedinthetableabovewerethosequoteddirectlybythecompanies.Definitionsofeligibilityvaryfromcompanytocompany.Eachoriginatorcompanyestablishesdifferentrestrictionstotheirofferofreducedprices,andclassifiescountriesaccordingtodifferentcategories.SomecompaniesresorttoLeast-DevelopedCountry(LDC)criteriadevelopedbytheUnitedNations,otherstotheUNDevelopmentProgramme’sHumanDevelopmentIndex(UNDPHDI),andothersstilltoWorldBankclassificationsconcerningcountryincome.
Thislackofuniformityleadstosignificantdifferencesintheeligibilityofacountryfordifferentproducts.
Forcompletedetailspleaserefertoannexes3-10.
Médecins Sans Frontières | July 2010��
ANNEx �: LEAST-DEVELOPED COUNTRIES (LDCS)Source:UnitedNations
http://www.un.org/special-rep/ohrlls/ldc/list.htm
Afghanistan;Angola;Bangladesh;Benin;Bhutan;BurkinaFaso;Burundi;Cambodia;CentralAfricanRepublic;Chad;Comoros;CongoDRC;Djibouti;EquatorialGuinea;Eritrea;Ethiopia;Gambia;Guinea;Guinea-Bissau;Haiti;Kiribati;LaoPDR;Lesotho;Liberia;Madagascar;Malawi;Maldives;Mali;Mauritania;Mozambique;Myanmar;Nepal;Niger;Rwanda;Samoa;SãoToméandPrincipe;Senegal;SierraLeone;SolomonIslands;Somalia;Sudan;Tanzania;Timor-Leste;Togo;Tuvalu;Uganda;Vanuatu;Yemen;Zambia.
ANNEx �: HUMAN DEVELOPMENT INDEx (HDI)Source:UnitedNationsDevelopmentProgramme(UNDP)
http://hdr.undp.org/en/media/hdr_20072008_en_complete.pdf
TheHumanDevelopmentIndexispublishedannuallyasapartofUNDP’sannualHumanDevelopmentReport.
Lowhumandevelopment:
Afghanistan;Benin;BurkinaFaso;Burundi;CentralAfricanRepublic;Chad;CongoDRC;Côted’Ivoire;Eritrea;Ethiopia;Gambia;Guinea;Guinea-Bissau;Liberia;Malawi;Mali;Mozambique;Niger;Rwanda;Senegal;SierraLeone;Timor-Leste;Togo;Zambia.
Mediumhumandevelopment:
Algeria;Angola;Armenia;Azerbaijan;Bangladesh;Belize;Bhutan;Bolivia;Botswana;Cambodia;Cameroon;CapeVerde;China;Comoros;Congo;Djibouti;DominicanRepublic;Egypt;ElSalvador;EquatorialGuinea;Fiji;Gabon;Georgia;Ghana;Guatemala;Guyana;Haiti;Honduras;India;Indonesia;Iran;Jamaica;Jordan;Kenya;Kyrgyzstan;LaoPDR;Lesotho;Madagascar;Maldives;Mauritania;Moldova;Mongolia;Morocco;Myanmar;Namibia;Nepal;Nicaragua;Nigeria;Pakistan;OccupiedPalestinianTerritories;PapuaNewGuinea;Paraguay;Philippines;
St.VincentandtheGrenadines;Samoa;SãoToméandPrincipe;SolomonIslands;SouthAfrica;SriLanka;Sudan;Suriname;Swaziland;Syria;Tanzania;Tajikistan;Thailand;Tonga;Tunisia;Turkmenistan;Uganda;Ukraine;Uzbekistan;Vanuatu;VietNam;Yemen.
ANNEx �: SUB-SAHARAN COUNTRIESSource:WorldBankcountryclassification
http://web.worldbank.org/WBSITE/EXTERNAL/DATASTATISTICS/0,contentMDK:20421402~pagePK:64133150~piPK:64133175~theSitePK:239419,00.html#Sub_Saharan_Africa
Angola;Benin;Botswana;BurkinaFaso;Burundi;Cameroon;CapeVerde;CentralAfricanRepublic;Chad;Comoros;Congo;CongoDRC;Côted’Ivoire;Eritrea;Ethiopia;Gabon;Gambia;Ghana;Guinea;Guinea-Bissau;Kenya;Lesotho;Liberia;Madagascar;Malawi;Mali;Mauritania;Mauritius;Mayotte;Mozambique;Namibia;Niger;Nigeria;Rwanda;SãoToméandPrincipe;Senegal;Seychelles;SierraLeone;Somalia;SouthAfrica;Sudan;Swaziland;Tanzania;Togo;Uganda;Zambia;Zimbabwe.
ANNEx �: WORLD BANk CLASSIFICATION OF ECONOMIESSource:WorldBank
http://web.worldbank.org/WBSITE/EXTERNAL/DATASTATISTICS/0,contentMDK:20421402~pagePK:64133150~piPK:64133175~theSitePK:239419,00.html
Thelistisupdatedeveryyearon1July.Thisversioniseffectivefrom1July2009.
Low-incomeeconomies:
Afghanistan;Bangladesh;Benin;BurkinaFaso;Burundi;Cambodia;CentralAfricanRepublic;Chad;Comoros;CongoDRC;Eritrea;Ethiopia;Gambia;Ghana;Guinea;Guinea-Bissau;Haiti;Kenya;Korea(DemocraticRepublic);Kyrgyzstan;LaoPDR;Liberia;Madagascar;Malawi;Mali;Mauritania;Mozambique;Myanmar;Nepal;Niger;Rwanda;Senegal;SierraLeone;Somalia;Tajikistan;Tanzania;Togo;Uganda;Uzbekistan;VietNam;Yemen;Zambia;Zimbabwe.
Lowermiddle-incomeeconomies:
Albania;Angola;Armenia;Azerbaijan;Belize;Bhutan;Bolivia;Cameroon;CapeVerde;China;Congo;Djibouti;Ecuador;Egypt;ElSalvador;Georgia;Guatemala;Guyana;Honduras;India;Indonesia;Iran;Iraq;Jordan;Kiribati;Kosovo;Lesotho;Maldives;MarshallIslands;Micronesia;Moldova;Mongolia;Morocco;Nicaragua;Nigeria;Pakistan;OccupiedPalestinianTerritories;PapuaNewGuinea;Paraguay;Philippines;Samoa;SãoToméandPrincipe;SolomonIslands;SriLanka;Sudan;Swaziland;Syria;Thailand;Timor-Leste;Tonga;Tunisia;Turkmenistan;Ukraine;Vanuatu.
Uppermiddle-incomeeconomies:
Algeria;AmericanSamoa;Argentina;Belarus;BosniaandHerzegovina;Botswana;Brazil;Bulgaria;Chile;Colombia;CostaRica;Croatia;Cuba;Dominica;DominicanRepublic;Fiji;Gabon;Grenada;Jamaica;Kazakhstan;Latvia;Lebanon;Libya;Lithuania;Macedonia;Malaysia;Mauritius;Mayotte;Mexico;Montenegro;Namibia;Palau;Panama;Peru;Poland;Romania;RussianFederation;Serbia;Seychelles;SouthAfrica;St.KittsandNevis;St.Lucia;St.VincentandtheGrenadines;Suriname;Turkey;Uruguay;Venezuela.
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Untangling the Web of ARV Price Reductions | Please check utw.msfaccess.org ��
ANNEx �: BRISTOL-MyERS SqUIBB ELIGIBLE COUNTRIESSource:ThefollowinglistsandnotesarefromcorrespondencewithBMS.
1stCategoryCountries:
Afghanistan;Angola;Bangladesh;Benin;Bhutan;BurkinaFaso;Burundi;Cambodia;Cameroon;CapeVerde;CentralAfricanRepublic;Chad;Comoros;Congo;CongoDRC;Côted’Ivoire;Djibouti;EquatorialGuinea;Eritrea;Ethiopia;Gabon;Gambia;Ghana;Guinea;Guinea-Bissau;Haiti;India;Kenya;LaoPDR;Liberia;Madagascar;Mali;Mauritania;Mauritius;Mongolia;Myanmar;Nepal;Nicaragua;Niger;Nigeria;Pakistan;PapuaNewGuinea;Rwanda;SãoToméandPrincipe;Senegal;Seychelles;SierraLeone;SolomonIslands;Somalia;Sudan;Tanzania;Timor-Leste;Togo;Tuvalu;Uganda;VietNam;Yemen.
2ndCategoryCountries:SouthernAfricancountries:
Botswana;Lesotho;Malawi;Mozambique;Namibia;SouthAfrica;Swaziland;Zambia;Zimbabwe.
ANNEx �: ABBOTT ELIGIBLE COUNTRIESSource:Abbott’sAccesstoHIVCareProgram
1stCategoryCountries:AfricaandLeast-Developedcountries:
Afghanistan;Algeria;Angola;Bangladesh;Benin;Bhutan;Botswana;BurkinaFaso;Burundi;Cambodia;Cameroon;CapeVerde;CentralAfricanRepublic;Chad;Comoros;Congo-Brazzaville;Côted’Ivoire;CongoDRC;Djibouti;EastTimor;Egypt;EquatorialGuinea;Eritrea;Ethiopia;Gabon;Gambia;Ghana;Guinea;Guinea-Bissau;Haiti;Kiribati;Kenya;LaoPDR;Lesotho;Liberia;Libya;Madagascar;Malawi;Maldives;Mali;Mauritania;Mauritius;Morocco;Mozambique;Myanmar;Namibia;Nepal;Niger;Nigeria;Rwanda;Samoa;SãoToméandPrincipe;Senegal;Seychelles;SierraLeone;SolomonIslands;Somalia;SouthAfrica;Sudan;Swaziland;Tanzania;Togo;Tunisia;Tuvalu;Uganda;Vanuatu;Yemen;Zambia;Zimbabwe.
2ndCategoryCountries:
Low-Incomeeconomies(excludingAfricaandtheLDCasdefinedbytheUN):
India;Kyrgyzstan;Mongolia;Pakistan;PapuaNewGuinea;Tajikistan;Uzbekistan;VietNam.
LowerMiddle-Incomeeconomies(excludingAfricaandtheLDCasdefinedbytheUN):
Albania;Armenia;Azerbaijan;Belarus;Bolivia;BosniaandHerzegovina;Brazil;China;Colombia;DominicanRepublic;Ecuador;ElSalvador;Fiji;Georgia;Guatemala;Guyana;Honduras;Indonesia;Jamaica;Jordan;Kazakhstan;FYR-Macedonia;MarshallIslands;Micronesia;Moldova;Montenegro;Nicaragua;Paraguay;Peru;Philippines;Serbia;SriLanka;Suriname;Syria;Thailand;Tonga;Turkmenistan;Ukraine.
ANNEx �: GILEAD ELIGIBLE COUNTRIESSource:GileadAccessProgram
http://www.gilead.com/enabling_access
1stCategoryCountries:
Low-IncomePricingTier
Afghanistan;Algeria;Angola;Anguilla;AntiguaandBarbuda;Bahamas;Bangladesh;Barbados;Belize;Benin;Bhutan;Bolivia;Botswana;BritishVirginIslands;BurkinaFaso;Burundi;Cambodia;Cameroon;CapeVerde;CentralAfricanRepublic;Chad;Comoros;Congo;CongoDRC;Côted’Ivoire;Cuba;Djibouti;Dominica;DominicanRepublic;Egypt;EquatorialGuinea;Eritrea;Ethiopia;Gabon;Gambia;Ghana;Grenada;Guatemala;Guinea;Guinea-Bissau;Guyana;Haiti;Honduras;India;Indonesia;Jamaica;Kenya;Kiribati;Kyrgyzstan;LaoPDR;Lesotho;Liberia;Libya;Madagascar;Malawi;Maldives;Mali;Mauritania;Mauritius;Moldova,Rep.of;Mongolia;Montserrat;Morocco;Mozambique;Myanmar;Namibia;Nauru;Nepal;Nicaragua;Niger;Nigeria;Pakistan;Palau;PapuaNewGuinea;Rwanda;St.KittsandNevis;St.Lucia;St.VincentandtheGrenadines;Samoa;SãoToméandPrincipe;Senegal;Seychelles;SierraLeone;SolomonIslands;Somalia;SouthAfrica;Sudan;Suriname;Swaziland;Syria;Tajikistan;Tanzania;Timor-Leste;Togo;TrinidadandTobago;Tunisia;TurksandCaicos;Tuvalu;Uganda;Ukraine;Uzbekistan;Vanuatu;VietNam;Yemen;Zambia;Zimbabwe.
2ndCategoryCountries:
LowerMiddle-IncomePricingTier
Albania;Armenia;Azerbaijan;Belarus;BosniaandHerzegovina;China;Ecuador;ElSalvador;Fiji;Georgia;Iran;Iraq;Jordan;Kazakhstan;Montenegro;Panama;Paraguay;Peru;Philippines;Serbia;SriLanka;Thailand;Tonga;Turkmenistan.
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ANNEx �0: MERCk & CO. INC. ELIGIBLE COUNTRIESSource:ThefollowinglistsandnotesarefromcorrespondencewithMerck.
Inquiriesaboutpricingforthefollowingcountrieswillbehandledonacase-by-casebasis:Iraq;MarshallIslands;Micronesia;Montenegro;Nauru;Korea(DPR);Palau.
Merck’sPricingPolicyforefavirenzandindinavir
1stCategoryCountries:
Afghanistan;Angola;Anguilla;AntiguaandBarbuda;Bangladesh;Belize;Benin;Bhutan;Botswana*;BurkinaFaso;Burundi;Cambodia;Cameroon;CapeVerde;CentralAfricanRepublic;Chad;Comoros;Congo;CongoDRC;Côted’Ivoire;Djibouti;Dominica;DominicanRepublic;EquatorialGuinea;Eritrea;Ethiopia;Gabon;Gambia;Ghana;Grenada;Guatemala;Guinea-Bissau;Guinea;Guyana;Haiti;Honduras;Jamaica;Kenya;Kiribati;LaoPDR;Lesotho;Liberia;Madagascar;Malawi;Maldives;Mali;Mauritania;Moldova;Mozambique;Myanmar;Namibia;Nepal;Niger;Nigeria;Pakistan;Panama;PapuaNewGuinea;Romania**;Russia;Rwanda;SãoToméandPrincipe;Senegal;SierraLeone;SolomonIslands;Somalia;SouthAfrica;St.KittsandNevis;St.Lucia;St.VincentandtheGrenadines;Sudan;Suriname;Swaziland;Tanzania;Thailand;Timor-Leste;Togo;TrinidadandTobago;Tuvalu;Uganda;Ukraine;Vanuatu;WesternSamoa;Yemen;Zambia;Zimbabwe.
2ndCategoryCountries:
Albania;Algeria;Armenia;Azerbaijan;Belarus;Bolivia;BosniaHerzegovina;Brazil;Bulgaria;China;Colombia;CostaRica;Ecuador;Egypt;ElSalvador;Estonia;Fiji;Georgia;India;Indonesia;Iran;Jordan;Kazakhstan;Kyrgyzstan;Latvia;Lebanon;Libya;Lithuania;Macedonia;Malaysia;Mauritius;Mexico;Mongolia;Morocco;Nicaragua;Oman;PalestinianTerritories;Paraguay;Peru;Philippines;SaudiArabia;Seychelles;SriLanka;Syria;Tajikistan;Tunisia;Turkey;Turkmenistan;Uzbekistan;Venezuela;VietNam.
*InBotswana,Merckprovidesindinavirandefavirenzfreeofcharge.
**DuetoaspecialpartnershipinRomania,Merckprovidesindinavirandefavirenzata‘no-profitprice’.
Merck’sPricingPolicyforraltegravir
1stCategoryCountries:
Afghanistan;Angola;Bangladesh;Benin;Bhutan;Botswana;BurkinaFaso;Burundi;Cambodia;Cameroon;CapeVerde;CentralAfricanRepublic;Chad;Comoros;Congo;CongoDRC;Côted’Ivoire;Djibouti;EquatorialGuinea;Eritrea;Ethiopia;Gabon;Gambia;Ghana;Guinea-Bissau;Guinea;Haiti;Kenya;Kiribati;LaoPDR;Lesotho;Liberia;Madagascar;Malawi;Maldives;Mali;Mauritania;Mozambique;Myanmar;Namibia;Nepal;Niger;Nigeria;Rwanda;SãoToméandPrincipe;Senegal;SierraLeone;SolomonIslands;Somalia;SouthAfrica;Sudan;Swaziland;Tanzania;Timor-Leste;Togo;Tuvalu;Uganda;Vanuatu;WesternSamoa;Yemen;Zambia;Zimbabwe.
2ndCategoryCountries:
Algeria;Armenia;Azerbaijan;Belize;Bolivia;Brazil**;China;Colombia;Dominica;DominicanRep.;Ecuador;Egypt;ElSalvador;Fiji;Georgia;Grenada;Guatemala;Guyana;Honduras;India;Indonesia;Iran;Jamaica;Jordan;Kazakhstan;Kyrgyzstan;Lebanon;Moldova;Mongolia;Morocco;Nicaragua;Pakistan;PalestinianTerritories;Peru;Philippines;St.Lucia;St.VincentandtheGrenadines;SriLanka;Suriname;Syria;Tajikistan;Thailand;Tunisia;Turkey;Turkmenistan;Ukraine;Uzbekistan;Venezuela;VietNam.
*InBotswana,Merckprovidesraltegravirfreeofcharge.
**MercknotesthatBrazil‘receivessignificantreducedpricingduetoextraordinarycommitmentintreatingHIV/AIDSpatients.’
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TDF/FTC/EFV300/200/600mg
1stCategoryCountries:
Afghanistan;Angola;AntiguaandBarbuda;Bangladesh;Belize;Benin;Bhutan;Botswana*;BurkinaFaso;Burundi;Cambodia;Cameroon;CapeVerde;CentralAfricanRepublic;Chad;Comoros;Congo;CongoDRC;Côted’Ivoire;Djibouti;Dominica;DominicanRepublic;EquatorialGuinea;Eritrea;Ethiopia;Gabon;Gambia;Ghana;Grenada;Guatemala;Guinea-Bissau;Guinea;Guyana;Haiti;Honduras;Jamaica;Kenya;Kiribati;LaoPDR;Lesotho;Liberia;Madagascar;Malawi;Maldives;Mali;Mauritania;Moldova;Mozambique;Myanmar;Namibia;Nepal;Niger;Nigeria;Pakistan;Panama;PapuaNewGuinea;Rwanda;SãoToméandPrincipe;Senegal;SierraLeone;SolomonIslands;Somalia;SouthAfrica;St.KittsandNevis;St.Lucia;St.VincentandtheGrenadines;Sudan;Suriname;Swaziland;Tanzania;Timor-Leste;Togo;TrinidadandTobago;Tuvalu;Uganda;Ukraine;Vanuatu;WesternSamoa;Yemen;Zambia;Zimbabwe.
2ndCategoryCountries:
Bolivia;Indonesia;Kyrgyzstan;Mauritius;Mongolia;Nicaragua;Seychelles;Syria;Tajikistan;Uzbekistan;VietNam.
Untangling the Web of ARV Price Reductions | Please check utw.msfaccess.org ��
Fordocumentationonpatents:
‘Determiningthepatentstatusofessentialmedicinesindevelopingcountries’,HealthEconomiesandDrugs,EDMSeriesNo.17,UNAIDS/WHO/MSF,2004.http://www.who.int/Intellectualproperty/submissions/MSFSubmissionWHO_EPM_PAR_2004.6.pdf
HIV/AIDSmedicinesandrelatedsupplies:Contemporarycontextandprocurement.Technicalguide.Chapter2andAnnexB.WorldBank,Washington,DC,2004http://siteresources.worldbank.org/INTPROCUREMENT/Resources/Technical-Guide-HIV-AIDS.pdf
‘Drugpatentsunderthespotlight.Sharingpracticalknowledgeaboutpharmaceuticalpatents’MSF,June2004.http://www.who.int/3by5/en/patents_2003.pdf
KnowledgeEcologyInternationalhttp://www.keionline.org,orhttp://www.cptech.org/ip/health/
Fordocumentationonquality:
PrequalificationProgrammemanagedbytheWorldHealthOrganization(WHO)http://apps.who.int/prequal/
ApprovedandTentativelyApprovedAntiretroviralsinAssociationwiththePresident’sEmergencyPlanhttp://www.fda.gov/InternationalPrograms/FDABeyondOurBordersForeignOffices/AsiaandAfrica/ucm119231.htm
Otherusefulwebsitesreferencedinthisdocument:
InternationalDispensaryAssociation(IDA)PriceIndicatorhttp://www.idafoundation.org/documents/ida_hiv_aids_aug_07_zondersnijlijnen.pdf
USFoodandDrugAdministrationOrangeBookhttp://www.fda.gov/cder/ob/
ANNEx ��: SUGGESTED RESOURCES FOR FURTHER INFORMATION:Fordocumentationonpricesquotedbycompanies:
UntanglingtheWebcanalsobefoundonlineatutw.msfaccess.org
BackissuesofUntanglingtheWebofpricereductions:apricingguideforthepurchaseofARVsfordevelopingcountriescanbefoundat:http://www.msfaccess.org/main/hiv-aids/untangling-the-web/untangling-the-web-archive/
SourcesandPricesofSelectedMedicinesandDiagnosticsforPeopleLivingwithHIV/AIDS(June2005and2006)http://www.who.int/medicines/areas/access/med_prices_hiv_aids/en/index.html
GlobalHIV/AidsEpidemicSelectionofAntiretroviralMedicationsProvidedunderU.S.EmergencyPlanIsLimited,January2005:http://pdf.dec.org/pdf_docs/Pcaab266.pdf
Fordocumentationonpricesreportedbycountries:
WHOGlobalPriceReportingMechanismhttp://www.who.int/3by5/amds/price/hdd/
TheGlobalFundPurchasePrice-Reporthttp://pqr.theglobalfund.org/PQRWeb/Reports/PurchasePriceReport.aspx
ManagementSciencesforHealth(MSH)InternationalDrugPriceIndicatorGuidehttp://erc.msh.org/mainpage.cfm?file=1.0.htm&id=1&temptitle=Introduction&module=DMP&language=English#top
WHOAFROregionEssentialMedicinesPriceIndicatorhttp://www.who.int/medicines/publications/afro-essential_med_price_indicator_nocover.pdf
CatalogueofUSFoodandDrugAdministrationApprovedDrugProductshttp://www.accessdata.fda.gov/scripts/cder/drugsatfda/
WHO.AntiretroviraltherapyforHIVinfectioninadultsandadolescents:recommendationsforapublichealthapproach-2006rev.Geneva:WHO;2006.http://www.who.int/hiv/pub/guidelines/artadultguidelines.pdf
WHO.Rapidadvice:antiretroviraltherapyforHIVinfectioninadultsandadolescents.Geneva:WHO;2009Nov.http://www.who.int/hiv/pub/arv/rapid_advice_art.pdf
AntiretroviralTherapyforHIVInfectioninInfantsandChildren:TowardsUniversalAccess:Recommendationsforapublichealthapproach2007.http://www.who.int/hiv/pub/guidelines/paediatric020907.pdf
UNICEFProcurementofHIV/AIDSRelatedSupplies.September2007http://www.unicef.org/supply/files/Procurement_of_HA_supplies(1).pdf
Biotechnology/PharmaceuticalsHIV/AIDSIndustryReport–April2005http://www.aethlonmedical.com/pdfs/IndustryReport.pdf
ClintonFoundationAntiretroviralPriceListhttp://www.clintonfoundation.org/files/chai_arv_priceList_april2010_english.pdf
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Médecins Sans Frontières | July 2010��
ANNEx ��: COMPANy CONTACTSAbbott:RobDintruffHIV/AccessDepartmentAbbottLaboratories,AbbottPlace219GolfClubTerraceConstantiaKloof1719,Johannesburg,SouthAfricaTel:+27118582000E-mail:[email protected]
Aurobindo:SharaddJainGMInternationalSales(Formulation)AurobindoPharmaLimitedSurvey#313,BachupallyQutubullapurMandalHyderabad-500072,IndiaTel:+914023044060Ext515(Office)E-mail:[email protected]:www.aurobindo.com
Boehringer Ingelheim:PhilipBaumCDCommunicationsTel:+49613277-2459Fax:+49613277-3829E-mail:[email protected]
Dr.MichaelRabbowCorpCommsCorporateAffairsTel:+49(6132)77-92701Fax:+49(6132)77-6601E-mail:[email protected]
Bristol-Myers Squibb:AllcountrieswiththeexceptionofSouthernAfrica:MrsMarie-AstridMercier,Coordinator,Globalaccessprogram,BMSoffice:ParisE-mail:[email protected]
SouthernAfrica:BMSoffice:JohannesburgMrArchieSmutsTel:+27114566527E-mail:[email protected]
Cipla: Mr.SanjeevGupteGeneralManager-ExportsCiplaLimitedTel:+912223021397(Direct)2309552123092891Fax:+912223070013/23070393/23070385E-mail:[email protected],[email protected]
Gilead: FororganisationsinAfrica,enquiriesshouldbedirectedto:GraemeRobertsonPhoneNumber:+442085872229E-mail:[email protected]:PhoneNumber:+16505225101E-mail:[email protected]:www.gilead.com/access_developing_world
Hetero: BhaveshShahHeteroDrugsLimited607/608MatharuArcard,PlotNo.32,SubhashRoad,VileParle(E),Mumbai–400057,IndiaTel:+912266910809(Office)Tel:+912266922829(Direct)Fax:+912226845709Mobile:+919821044912E-mail:[email protected]:www.heterodrugs.com
Huahai: Mr.CaiMinDaViceGeneralManagerXunqiao,Linhai,Zhejiang317024,ChinaTel:+8657685991657(Headquarters);Tel:+862153086386(Shanghaioffice)E-mail:[email protected]
Matrix: AvrindKandaGeneralManager,BusinessDevelopmentAntiRetroviralFinishedDosagesMatrixLaboratoriesLimited1-1-151/1,VFloor,SairamTowersAlexanderRoad,Secunderabad-500003AndhraPradesh,IndiaTel:+914027700363Fax:+919948220256
SunilGaurBusinessDevelopmentMatrixLaboratoriesLimited1-1-151/1,VIFloor.SairamTowersAlexanderRoadSecunderabad-500003AndhraPradesh,IndiaTel:+914027700363/+914055327722Mobile:+919948092653Fax:+914066336401
Merck: MargalitEdelmanManager,GlobalPublicPolicyMerck&Co.Inc.WS2A-65,OneMerckDrive,P.O.Box100WhitehouseStation,NJ08889-0100Tel:(908)4233112Fax:(908)7351391E-mail:[email protected]
Ranbaxy: ShaileshPednekarGeneralManager-GlobalTherapyManagementandARVBusinessPlotNo90Sector32,Gurgaon122001,IndiaTel:+91.124.41.85.911(DIR),9141.35.000ext5911,+919810263679(mobile)Fax:+91.124.41.66.035E-mail:[email protected]
Roche: SandraTorrianiDemandManagerPTBFPMIF.Hoffmann-LaRocheLtdBuilding237/2.31CH-4070Basel,SwitzerlandTel:+41616889390Fax:+41616871815E-mail:[email protected]
Strides: Mrs.AlokaSenguptaPresident–MarketingStridesHouse,BannerghattaRoadBangalore560076,IndiaTel:+91-80-66580748Mobile:+919845024470Fax:+91-80-66580800E-mail:[email protected]
Dr.RajivAlexVice–President–AT&MStridesHouse,BannerghattaRoadBangalore560076,IndiaTel:+91-80-66580103Mobile:+919632925925Fax:+91-80-66580800E-mail:[email protected]
Tibotec: LucDenysSeniorDirectorWorldwideAccessPrograms,VirologyTibotec-VircoComm.VaTel:+32(0)15.461.018Fax:+32(0)15.401.259Mobile:+32(0)479.96.43.42
ViiV: ScottPurdonPhDDirectorAccessandGovernmentAffairsViiVHealthcare980GreatWestRoadBrentfordMiddlesex,TW89GSUKTel:+442083806228
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ANNEx ��: THE CLINTON FOUNDATION ANTIRETROVIRAL PRICE LIST
(AS OF APRIL �0�0)
SUPPLIERS & PRODUCTSCHAIhasagreementswithsevenmanufacturersofARVformulations,activepharmaceuticalingredientsand/orpharmaceuticalintermediates:AurobindoPharma,CiplaLtd.,HeteroDrugs,MacleodsPharmaceuticals,MatrixLaboratories,RanbaxyLaboratoriesandStridesArcolabs.TheARVsincludedinCHAI’spricingagreementsare:abacavir(ABC),atazanavir(ATV),efavirenz(EFV),emtricitabine(FTC),lamivudine(3TC),lopinavir/ritonavir(LPV/r),nevirapine(NVP),stavudine(d4T),tenofovir(TDF)andzidovudine(AZT).
TERMS & CONDITIONS PriceslistedbelowareavailabletocountriesparticipatingintheCHAIProcurementConsortium,whichcurrentlyincludesover70nations.ThesepricesapplytoprocurementsbynationalgovernmentsthataremembersoftheCHAIProcurementConsortium,ororganizationsprocuringonbehalfofmembergovernments,tosupportpubliccareandtreatmentprograms.Productsshouldbepurchaseddirectlyfrompartnersuppliersorthroughprocurementagentsrepresentingtheaforementionedprograms.
ForTDFproductsofferedbysuppliersunderavoluntarylicensefromGilead,indicatedpricingisavailableonlytocountriescoveredunderthevoluntarylicense.PleasecontactNeerajMohanatnmohan@clintonfoundation.orgwithanyquestionsrelatedtothisissue.AccesstoCHAIpricesassumespromptpaymentfollowingtheshipmentoforders.Purchasersissuingrequestsforpricequotesand/ortenderstowhichCHAIpartnersuppliersareinvitedtorespondshouldreferencemembershipintheCHAIProcurementConsortium,butrequestsandtendersneednotberestrictedtoCHAIpartnersuppliers.
PRICESCHAIpricesrepresentpriceceilingsatorbelowwhichtheindicatedsuppliersmustpricetheirproductswhensellingorcommunicatingpricequotesforthespecifiedproductstomembersoftheCHAIProcurementConsortium.Inestablishingpriceceilings,CHAIaimstoofferthelowestavailablepricestoConsortiummemberswhileensuringthatproductsareavailablefrommorethanonepartnersupplierwhereverpossible.PriceslistedbelowareFCAAirportfromthepointofexport.Perpersonperyearpricesforpediatricformulationsaredeterminedbasedontherecommendeddailydosingfora10kgchild(unlessaformulationisnotrecommendedfora10kgchild,inwhichcasetheannualpriceiscalculatedbasedondosingforanapplicableweightband).
qUALITyCHAIiscommittedtothesustainablesupplyofhigh-qualityARVs,consistentwiththespecificationsofdossiersapprovedbytheWorldHealthOrganization(WHO),U.S.FoodandDrugAdministration(U.S.FDA),orastringentregulatoryauthority(SRA)asdefinedbytheInternationalConferenceonHarmonization(ICH).Inthelistonpages90and91,footnotesspecifytheapplicablequalityassurancestatusforeachformulation:(1)ApprovedbytheWHOPrequalificationProgramme;(2)ApprovedbytheU.S.FDAorotherSRA;(3)SubmittedtotheWHO,U.S.FDAorotherSRAforreviewandrecommendedforprocurementbyExpertReviewPanel(ERP)ofTheGlobalFund;(4)SubmittedtotheWHO,U.S.FDAorotherSRAforreviewbutnotyetrecommendedbyERP.
The Clinton Health Access Initiative (CHAI) supports national governments to expand high-quality care and treatment to people living with HIV/AIDS. CHAI offers reduced prices for antiretrovirals (ARVs) to members of its Procurement Consortium.
Médecins Sans Frontières | July 2010�0
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ADULT PRODUCTS CEILING PRICE (USD) SUPPLIER
Nameandstrength Packaging PerYear PerPack PerUnit Aurobindo Cipla Hetero MacLeods Matrix Ranbaxy
3TC(150mg)HDPEbottle60tablets
$32 $2.67 $0.044 a1,2 a1 a1 a2 a1,2
ABC(300mg)HDPEbottle60tablets
$222 $18.50 $0.308 a2 a1,2 a4 a1,2
AZT(300mg)HDPEbottle60tablets
$93 $7.75 $0.129 a1,2 a1 a2 a1,2 a1,2
AZT(300mg)+3TC(150mg)
HDPEbottle60tablets
$110 $9.17 $0.153 a1,2 a1,2 a1,2 a2
AZT(300mg)+3TC(150mg)+NVP(200mg)
HDPEbottle60tablets
$140 $11.67 $0.194 a2 a1,2 a1,2
ATV(300mg)*HDPEbottle30capsules
$265 $22.08 $0.736 a3
d4T(30mg)HDPEbottle60capsules
$24 $2.00 $0.033 a1,2 a2 a1,2 a1
d4T(30mg)+3TC(150mg)
HDPEbottle60tablets
$45 $3.75 $0.063 a1 a1,2 a1,2
d4T(30mg)+3TC(150mg)+NVP(200mg)
HDPEbottle60tablets
$79 $6.58 $0.110 a1 a1,2 a1 a1
EFV(600mg)HDPEbottle30tablets
$75 $6.25 $0.208 a1,2 a1,2
LPV/r(200/50mg)HDPEbottle120tablets
$440 $36.67 $0.306 a2 a2 a4 a1,2
NVP(200mg)HDPEbottle60tablets
$37 $3.08 $0.051 a1,2 a1,2 a1,2 a2 a1,2 a1,2
RTV(100mg)heat-stable*
HDPEbottle30tablets
$90 $7.50 $0.250 a4
TDF(300mg)HDPEbottle30tablets
$87 $7.25 $0.242 a2 a1,2 a2 a1,2
TDF+3TC(300/300mg)*
HDPEbottle30tablets
$110 $9.17 $0.306 a2 a2
TDF+FTC(300/200mg)HDPEbottle30tablets
$140 $11.67 $0.389 a2 a2
TDF+3TC+EFV(300/300/600mg)
HDPEbottle30tablets
$200 $16.67 $0.556 a2
TDF+FTC+EFV(300/200/600mg)
HDPEbottle30tablets
$229 $19.10 $0.637 a2
CLINTON HEALTH ACCESS INITIATIVE — ANTIRETROVIRAL (ARV) PRICE LIST
*CHAIhasnegotiatedapriceofUSD$425perpersonperyearforaco-packagedonce-dailysecond-lineregimencontainingATV,heat-stableRTVandafixeddosecombinationofTDF+3TC.Thisproductislikelytobeavailableforprocurementinlate2010.
Untangling the Web of ARV Price Reductions | Please check utw.msfaccess.org ��
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IST
PEDIATRIC PRODUCT CEILING PRICE (USD) SUPPLIER
Nameandstrength Packaging PerYear PerPack PerUnit Aurobindo Cipla Matrix Strides
3TC(50mg/5ml)HDPEbottle240ml
$25 $1.65 $0.007 a2 a1,2
ABC(20mg/ml)HDPEbottle240ml
$203 $13.53 $0.056 a2 a1
ABC60mgHDPEbottle60tablets
$126 $5.25 $0.088 a2 a1
ABC(60mg)+3TC(30mg)HDPEbottle60tablets
$168 $7.00 $0.117 a2 a1
AZT(50mg/5ml)HDPEbottle240ml
$57 $1.90 $0.008 a2 a1,2
AZT(100mg)HDPEbottle100capsules
$35 $4.80 $0.048 a2 a1
AZT(60mg)+3TC(30mg)HDPEbottle60tablets
$80 $3.34 $0.056 a2 a1
AZT(60mg)+3TC(30mg)+NVP(50mg)
HDPEbottle60tablets
$102 $4.25 $0.071 a1
d4T(1mg/ml)HDPEbottle200ml
$47 $1.30 $0.007 a2 a2
d4T(15mg)HDPEbottle60capsules
$16 $1.35 $0.023 a2
d4T(20mg)HDPEbottle60capsules
$8 $1.40 $0.023 a2
d4T(6mg)+3TC(30mg)HDPEbottle60tablets
$46 $1.90 $0.032 a2
d4T(12mg)+3TC(60mg)HDPEbottle60tablets
$40 $3.30 $0.055 a2
d4T(6mg)+3TC(30mg)+NVP(50mg)
HDPEbottle60tablets
$55 $2.30 $0.038 a1,2
d4T(12mg)+3TC(60mg)+NVP(100mg)
HDPEbottle60tablets
$52 $4.30 $0.072 a1,2
EFV(50mg)HDPEbottle30tablets
$27 $2.24 $0.075 a2 a2
EFV(200mg)HDPEbottle90capsules
$43 $10.75 $0.119 a2 a2 a2
EFV(200mg)HDPEbottle90scoredtablets
$43 $10.75 $0.119 a1,2
LPV/r(100/25mg)HDPEbottle120tablets
$220 $18.33 $0.153 a1
NVP(50mg/5ml)HDPEbottle240ml
$53 $1.75 $0.007 a1,2 a1
CLINTON HEALTH ACCESS INITIATIVE — ANTIRETROVIRAL (ARV) PRICE LIST
Médecins Sans Frontières | July 2010��
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Untangling the Web of ARV Price Reductions | Please check utw.msfaccess.org ��
3TC:lamivudine;nucleosideanaloguereversetranscriptaseinhibitor.
ABC:abacavir;nucleosideanaloguereversetranscriptaseinhibitor.
AIDS:AcquiredImmuneDeficiencySyndrome.
ALP:AIDSLawProject.
ANVISA:AgênciaNacionaldeVigilânciaSanitária(NationalHealthSurveillanceAgencyBrazil).
API:activepharmaceuticalingredient.
ARIPO:AfricanRegionalIntellectualPropertyOrganisation.TherearecurrentlysixteenstateswhicharepartytotheLusakaAgreementandthereforemembersofARIPO.Theseare:Botswana,theGambia,Ghana,Kenya,Lesotho,Malawi,Mozambique,Namibia,SierraLeone,Somalia,Sudan,Swaziland,Tanzania,Uganda,ZambiaandZimbabwe.
ARV:Antiretroviral.
ATV:atazanavir,proteaseinhibitor.
AZT:zidovudine(alsoabbreviatedtoZDV),nucleosideanaloguereversetranscriptaseinhibitor.
BI:BoehringerIngelheim.
BMS:Bristol-MyersSquibb.
Category1:Inthisdocument,‘Category1’isusedtodescribethosecountriesthatareeligibleforthemostdiscountedpriceofferedbyacompany.
Category2:Inthisdocument,‘Category2’isusedtodescribethosecountriesthatarenoteligibleforthelowestpricesreservedforcategory1countries,butareneverthelessofferedadiscountbycompanies.Crucially,thisdiscountisusuallyconsiderablysmallerthanthediscountofferedtocategory1countries.
CCR5:chemokinecoreceptor5.
CF:ClintonFoundation.
AB
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ABBREVIATIONS
CHAI:ClintonFoundationHealthAccessInitiative.Since2002,theClintonFoundationHealthAccessInitiative(CHAI)hasassistedcountriesinimplementinglarge-scale,integratedcare,treatmentandpreventionprogrammes.
CHF:Swissfranc.
CIF:‘CostInsuranceandFreight’.Acommercialterm(incoterm)meaningthatthesellerdeliversoncethegoodspasstheship’srailintheportofshipment.ThesellermustpaythecostsandfreightnecessarytobringthegoodstothenamedportofdestinationBUTtheriskoflossordamagetothegoods,aswellasanyadditionalcostsduetoeventsoccurringafterthetimeofdelivery,aretransferredfromthesellertothebuyer.
CIP:‘CarriageandInsurancepaidto...’.Acommercialterm(incoterm)meaningthatthesellerdeliversthegoodstothecarriernominatedbyhim,butthesellermustinadditionpaythecostofcarriagenecessarytobringthegoodstothenameddestination.Thismeansthatthebuyerbearsalltherisksandanyadditionalcostsoccurringafterthegoodshavebeendelivered.However,inCIPtheselleralsohastoprocureinsuranceagainstthebuyer’sriskoflossofordamagetothegoodsduringcarriage.Consequently,thesellercontractsforinsuranceandpaystheinsurancepremium.
CL:compulsorylicence.
d4T:stavudine;nucleosideanaloguereversetranscriptaseinhibitor.
ddl:didanosine;nucleosideanaloguereversetranscriptaseinhibitor.
DDU:‘Delivereddutyunpaid’.Acommercialterm(incoterm)meaningthatthesellerdeliversthegoodstothebuyer,notclearedforimport,andnotunloadedfromanyarrivingmeansoftransportatthenamedplaceofdestination.Thesellerhastobearthecostsandrisks
involvedinshippingthegoods,otherthan,whereapplicable,any‘duty’(whichincludestheresponsibilityfortherisksofthecarryingoutofthecustomsformalities,andthepaymentofformalities,customsduties,taxesandothercharges)forimportinthecountryofdestination.Such‘duty’hastobebornebythebuyeraswellasanycostsandriskscausedbyhisfailuretoclearthegoodsfortheimporttime.
DRV:darunavir,proteaseinhibitor.
EC:enteric-coated.
EFVorEFZ:efavirenz;non-nucleosideanaloguereversetranscriptaseinhibitor.
EMA:EuropeanMedicinesAgency.FormerlyEuropeanAgencyfortheEvaluationofMedicinalProducts.
EML:EssentialMedicinesList.FirstpublishedbyWHOin1977,itservestoidentifyalistofmedicines,whichprovidesafeandeffectivetreatmentforinfectiousandchronicdiseasesaffectingthevastmajorityoftheworld’spopulation.The16thUpdatedListwaspublishedinMarch2009andincludes14antiretroviralsandfivefixed-dosecombinations.
EU:EuropeanUnion.
EXW:‘Ex-works’.Acommercialterm(incoterm)meaningthatthesellerdeliverswhenheplacesthegoodsatthedisposalofthebuyerattheseller’spremisesoranothernamedplace(i.e.works,factory,warehouseetc.)notclearedforexportandnotloadedonanycollectingvehicle.
FDA:UnitedStatesFoodandDrugAdministration.
FDC:fixed-dosecombination–multipledrugscombinedinasinglepill.
Médecins Sans Frontières | July 2010�00
FOB:‘Freeonboard’.Acommercial(incoterm)termmeaningthatthesellerdeliverswhenthegoodspasstheship’srailatthenamedportofshipment.Thismeansthatthebuyerhastobearallcostsandrisksoflossordamagetothegoodsfromthatpoint.TheFOBtermrequiresthesellertoclearthegoodsforexport.
FPV:fosamprenavir;proteaseinhibitor.
FTC:emtricitabine;nucleosideanaloguereversetranscriptaseinhibitor.
Genericdrug:AccordingtoWHO,apharmaceuticalproductusuallyintendedtobeinterchangeablewiththeoriginatorproduct,whichisusuallymanufacturedwithoutalicensefromtheoriginatorcompany.
GPRM:WHOGlobalPriceReportingMechanism.AdatabasecontainingpricespaidbyUNICEF,theInternationalDispensaryAssociation(IDA),ManagementSciencesforHealth(MSH)/Deliver,andtheGlobalFundtoFightAIDS,TuberculosisandMalaria.
GSK:GlaxoSmithKline.
HDI:HumanDevelopmentIndex.AsummarycompositeindexcompiledbyUNDP,thatmeasuresacountry’saverageachievementsinthreebasicaspectsofhumandevelopment:longevity(orlifeexpectancyatbirth),knowledge(oradultliteracyrateandenrolmentineducation),andadecentstandardofliving(grossdomesticproductpercapita).
HIV:HumanImmunodeficiencyVirus.
IDV:indinavir;proteaseinhibitor.
IRBM:InstituteforResearchinMolecularBiology.
LDCs:Least-DevelopedCountries,accordingtoUnitedNationsclassification.
LPV/r:lopinavir/ritonavir;boostedproteaseinhibitor.
MSD:MerckSharp&Dome(Merck&Co.,Inc.)
MSF:MédecinsSansFrontières,DoctorsWithoutBorders.
MVC:maraviroc;entryinhibitor.
AB
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S NDRA:NationalDrugRegulatoryAuthority.
NFV:nelfinavir;proteaseinhibitor.
NGO:Non-GovernmentalOrganisation.
NIH:NationalInstitutesofHealth.
NNRTI:Non-NucleosideReverseTranscriptaseInhibitor.
NRTI:NucleosideAnalogueReverseTranscriptaseInhibitor.
NtRTI:NucleotideReverseTranscriptaseInhibitor.
NVP:nevirapine;non-nucleosideanaloguereversetranscriptaseinhibitor.
OAPI:OrganisationAfricainedelaPropriétéIntellectuelle(AfricanIntellectualPropertyOrganisation).MemberstatesincludeBenin,BurkinaFaso,Cameroon,CentralAfricanRepublic,Chad,Congo,Côted’Ivoire,Gabon,Guinea,Guinea-Bissau,EquatorialGuinea,Mali,Mauritania,Niger,Senegal,Togo.
PEPFAR:President’sEmergencyPlanforAIDSRelief,aUnitedStatesprogrammetofightHIV/AIDSindevelopingcountries.
PI:ProteaseInhibitor.
PLHA:PeopleLivingWithHIV/AIDS.
PMTCT:PreventionofMother-to-ChildTransmission.
ppy:perpatientperyear.
r:low-doseritonavir,usedasabooster.
R&D:ResearchandDevelopment.
RAL:raltegravir;integraseinhibitor.
RTV:ritonavir;proteaseinhibitor.
SQV:saquinavir;proteaseinhibitor.
TAC:TreatmentActionCampaign.
TB:tuberculosis.
TDF:tenofovirdisoproxilfumarate;nucleotidereversetranscriptaseinhibitor.
TPV:tipranavir;proteaseinhibitor.
TRIPS:Trade-relatedAspectsofIntellectualPropertyRights.
UN:UnitedNations.
UNAIDS:UnitedNationsJointCosponsoredProgrammeonHIV/AIDS.Createdin1996,tolead,strengthenandsupportanexpandedresponsetotheHIV/AIDSepidemic.ThesixoriginalcosponsorsareUNICEF,UNDP,UNFPA,UNESCO,WHOandtheWorldBank.UNDCPjoinedinApril1999.
UNDP:UnitedNationsDevelopmentProgramme.
UNITAID:isaninternationaldrugpurchasefacilitythatwasestablishedin2006byBrazil,Chile,France,NorwayandtheUnitedKingdomandnowincludes27countriestoprovidenewsourcesoffundingtofightHIV/AIDS,malariaandtuberculosis.
USFDA:UnitedStatesFoodandDrugAdministration.
VL:voluntarylicence.
WHO:WorldHealthOrganization.
WHOGPRM:WHOGlobalPriceReportingMechanism.
WTO:WorldTradeOrganization.
ZDV:zidovudine(alsoabbreviatedtoAZT);nucleosideanaloguereversetranscriptaseinhibitor.
Untangling the Web of ARV Price Reductions | Please check utw.msfaccess.org
DISCLAIMER:‘UntanglingtheWebofPriceReductions’isapricingguideandcannotberegardedasacompanypricelist.Itiscrucialthatanypurchaserverifypricesandavailabilityaswellasqualitystatusdirectlywiththesupplierbeforeprocurement.MédecinsSansFrontièreshasmadeeveryefforttoensuretheaccuracyofpricesandotherinformationpresentedinthisreport,butMSFmakesnorepresentationsorwarranties,eitherexpressedorimplied,astotheiraccuracy,completenessorfitnessforaparticularpurpose.InclusionofaproductinthisdocumentdoesnotindicateMSFpurchasesorusestheproduct.Informationonpatentstatusoftheproductsmentionedinthisguideisindicativeonlyandnotexhaustive,andshouldbeverifiedwithrelevantnationalpatentofficeswhenusedforotherthanreasonsofgeneralinformation.
ACkNOWLEDGEMENTS:
Frontandbackcoverphotos:BrendanBannon
Design/artwork:ACWLtd+44(0)2083924330www.acw.uk.com
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