Dr Andrew Hill, Pharmacology and Therapeutics, Liverpool University, UK

Treatment of HIV and Hepatitis C: branded versus

generic medicines

Africa, 1999: mass treatment for HIV/AIDS is not feasible

2

A key moment in the history of HIV

“My generics company can manufacture HIV antiretrovirals for a dollar per day”

Dr Yussef Hamied Cipla, G8 summit, 2000

3

Russia and UNAIDS 90-90-90: How many people would be on treatment for HIV?

Ref: The Joint United Nations Programme on HIV/AIDS. 90-90-90 An ambitious treatment target to help end the AIDS epidemic. 2014; JC2684 (Numbers as of March 2015) How Aids Changed Everything. Fact Sheet. UNAIDS 2015. MDG 6: 15 YEARS, 15 LESSONS OF HOPE FROM THE AIDS RESPONSE July 2015.

Target 1: 90% of HIV+ people diagnosed

Target 2: 90% of diagnosed people on ART

Target 3:90% of people on ART with HIV RNA suppression

Cascade of HIV care – Russia 2013

Ref: Pokrovskaya, A., et al The cascade of HIV care in Russia, 2011–2013. Journal of the International AIDS Society 2014;17(4). http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4224814/pdf/JIAS-17-19506.pdf

Minimum Costs of ARV treatments: HIVGREEN – FULLY GENERIC WORLDWIDE IN 2017/8

RED – STILL PATENTED TO 2025+ : VOLUNTARY LICENSES

______________________________________________________________

Combination Estimated price / year

______________________________________________________________

TDF/3TC/ATV/r $279

TDF/FTC/ELV/c $184

ABC/3TC/DTG $179

TDF/FTC/EFV600 $144

TDF/3TC/EFV600 $130

TDF/3TC/EFV400 $100

TAF/3TC/DTG $60

DTG/3TC $46

_______________________________________________________

HIV Patent Expiry dates: 2015-2029

11 years (2015-2026) when many drugs are available as individual generics, but co-formulated versions are still on patent

2014: ZDV, 3TC, NVP, EFV, RTV – already generic

2016: ABC, LPV/r2017: TDF, ATV/r, DRV/r

2019: ABC/3TC (Kivexa)2021: ETR2024: TDF/FTC (Truvada)2025: Raltegravir2026: TDF/3TC/EFV (Atripla), TDF/FTC/RPV (Complera), 2029: ABC/3TC/DTG (Triumeq), TAF/FTC/ELV/c

Ref: Medecins Sans Frontieres 2014: Untangling the web of ARV price reductions

Voluntary licenses

Some pharmaceutical companies allow cheap generics to be sold in certain low and middle income countries, with voluntary licenses

Russia and Eastern European countries are not included in most of these agreements

As a result, prices in Russia and Eastern Europe can be unaffordable

DOLUTEGRAVIR VOLUNTARY LICENSE COVERAGE

ATAZANAVIR VOLUNTARY LICENSE COVERAGE

DARUNAVIR VOLUNTARY LICENSE COVERAGE

PRICING: DARUNAVIR INSIDE & OUTSIDE SUB-SAHARAN AFRICA

Dosage strength: DRV 600mg and 300mg.

Drug Russian price(US $)

Access price (US $)

Price difference

Basic patent expiry (Russia)

Lamivudine $286 $29 +886% 2010

Abacavir $778 $140 +456% 2010

Darunavir $4695 $737 +537% 2013

Efavirenz $135 $46 +193% 2013

Ritonavir $310 $91 +241% 2014

Atazanavir/r $1204 $201 +499% 2017

Prices in Russia from Государственный реестр лекарственных средств http://grls.rosminzdrav.ru/PriceLims.aspx (TDF, 3TC, r, RAL) and ITPCru http://itpcru.org/2015/12/01/analiz-gosudarstvennyh-zakupok-arv-preparatov-pereboi-yanvar-noyabr-2015/ (TDF/FTC, ABC, ATV/r, LPV/r, DRV, DTG, EFV).All global lowest prices from Clinton Health Access Initiative Reference Price List 2015, except: darunavir (South African Medicine Prices Registry), raltegravir (MSF Untangling The Web 17th Edition), dolutegravir (launch price in South Africa). ‘Basic patent’ refers to the composition of matter patent. Additional patent expiry dates of interest given in brackets. Patent expiry dates: Medicines Patent Pool.

Drug Russian price(US $)

Access price (US $)

Price difference

Basic patent expiry (Russia)

Lopinavir/r $1434 $256 +460% 2017

Tenofovir DF $1172 $49 +2292% 2018

Raltegravir $6424 $675 +852% 2022

Tenofovir/FTC $2313 $68 +3301% 2024

Dolutegravir $4940 $600 ($38) +723% 2026

Prices in Russia from Государственный реестр лекарственных средств http://grls.rosminzdrav.ru/PriceLims.aspx (TDF, 3TC, r, RAL) and ITPCru http://itpcru.org/2015/12/01/analiz-gosudarstvennyh-zakupok-arv-preparatov-pereboi-yanvar-noyabr-2015/ (TDF/FTC, ABC, ATV/r, LPV/r, DRV, DTG, EFV).All global lowest prices from Clinton Health Access Initiative Reference Price List 2015, except: darunavir (South African Medicine Prices Registry), raltegravir (MSF Untangling The Web 17th Edition), dolutegravir (launch price in South Africa). ‘Basic patent’ refers to the composition of matter patent. Additional patent expiry dates of interest given in brackets. Patent expiry dates: Medicines Patent Pool.

Top 10 HIV epidemics worldwide______________________________________________________________

Country HIV Epidemic Cost of TDF/FTC/EFV

______________________________________________________________

South Africa 6.3 million $110

Nigeria 3.4 million $110

India 2.1 million $300

Zimbabwe 1.6 million $110

Mozambique 1.5 million $110

Uganda 1.5 million $110

Tanzania 1.5 million $110

Kenya 1.4 million $110

Russia 1.4 million $2448

Zambia 1.2 million $110

_______________________________________________________

Top 10 HIV epidemics worldwide______________________________________________________________

Country HIV Epidemic Agreed price: TDF/FTC/DTG

______________________________________________________________

South Africa 6.3 million $110

Nigeria 3.4 million $110

India 2.1 million $300

Zimbabwe 1.6 million $110

Mozambique 1.5 million $110

Uganda 1.5 million $110

Tanzania 1.5 million $110

Kenya 1.4 million $110

Russia 1.4 million $7253

Zambia 1.2 million $110

_______________________________________________________

HIV Patent Expiry dates: 2015-2029

11 years (2015-2026) when many drugs are available as individual generics, but co-formulated versions are still on patent

2014: ZDV, 3TC, NVP, EFV, RTV – already generic

2016: ABC, LPV/r2017: TDF, ATV/r, DRV/r

2019: ABC/3TC (Kivexa)2021: ETR2024: TDF/FTC (Truvada)2025: Raltegravir2026: TDF/3TC/EFV (Atripla), TDF/FTC/RPV (Complera), 2029: ABC/3TC/DTG (Triumeq), TAF/FTC/ELV/c

Ref: Medecins Sans Frontieres 2014: Untangling the web of ARV price reductions

Prices for co-formulations can be much higher – switch to single pills

TDF/FTC/EFV

TDF/FTC/RPV

TDF/FTC/ELV/c

ABC/3TC/DTG

Generic TDF or ABC

Generic 3TC

Generic EFV or PI/r

Patented pillOver $3000/year

Generic pills< $300/year

Russia, Thailand and Brazil

All three countries excluded from voluntary licenses

Thailand and Brazil make their own antiretrovirals

Issue compulsory licenses on pharmaceuticals – overturned the patents to allow access to medicine.

Thailand and Brazil have among the highest HIV treatment coverage rates worldwide.

How much would it cost to acheive 90-90-90 in Russia?

___________________________________________________________________

1.1 million people Current prices Access prices

__________________________________________________________________

TDF/FTC/EFV $2.7 billion $121 million

184 billion roubles 816 million

roubles

TDF/FTC/DTG $8.0 billion $121 million

544 billion roubles 816 million

roubles

____________________________________________________________Assumes current costs:

TDF/FTC/EFV in Russia = $2448 / year, vs access price $110

TDF/FTC/DTG in Russia = $7453/year, vs access price $110

Entecavir for Hepatitis Bone year’s supply (0.2g)

Entecavir for Hepatitis Bcost per person/year by country

Entecavir (Baraclude)

US price: $15,111

Cost price: $36

Prices for Hepatitis C DAAsDrug Calculated

target price for 12-week treatment

Current global lowest

Current Russian price

Sofosbuvir $95 $300 -

Ledipasvir $136 - -

Daclatasvir $17 $153 $4700

Velpatasvir $119-154 - -

Current costs of sofosbuvir, per person (12 weeks)

USA USA* UK Spain Brazil LMICs Generic Mini

*discount

Cos

t (U

S $

)

Top 10 Hepatitis C epidemics worldwide______________________________________________________________

Country HCV Epidemic Treatments

______________________________________________________________

China 29.8 million Local production

India 18.2 million Voluntary licenses

Egypt 11.8 million Voluntary licenses

Pakistan 9.7 million Voluntary licenses

Indonesia 9.4 million Voluntary licenses

Russia 5.8 million High prices

USA 5.4 million High prices

DR Congo 4.0 million Voluntary licenses

Nigeria 3.3 million Voluntary licenses

Japan 3.0 million High prices

_______________________________________________________

Patented vs Generic DAAs in the UK

Harvoni45,000 Euros

Generic SOF/DCV900 Euros

SOFOSBUVIR VOLUNTARY LICENSE & REGISTRATION

Data: Gilead License Factsheet, Aug 2015. Gilead Sovaldi registration, May 2015.

No voluntary license

Voluntary license, registered

Voluntary license, not registeredVoluntary license, registration pending/filed

Gilead sales and profits

Cumulative sales of sofosbuvir and Harvoni to end 2015: $31.5 billion

Profits in 2015: $18 billion

The new $90 $90 $90

There could be standard prices for HIV, Hepatitis B and Hepatitis C worldwide

$90 per year to treat HIV

$90 per year to treat Hepatitis B

$90 for a 12 week course of treatment to cure Hepatitis C

Conclusions

To achieve UNAIDS 90-90-90 targets for HIV, and mass treatment for Hepatitis B and C, Russia would need to become like Thailand and Brazil

- Harder negotiations on drug pricing with pharmaceutical companies

- Compulsory licensing if necessary, imports from India

- Mass Local production of antiretrovirals if necessary

It is possible to treat large numbers of people, but only with huge reductions in treatment costs.