Indian Council of Medical Research
Meeting withCommission on Intellectual Property Rights, Innovation and Public Health
Prof N K GangulyDirector General
Indian Council of Medical ResearchNew Delhi, India
Indian Council of Medical Research
The ‘India Advantage’
150
350
15 20 40
400
050
100150200250300350400450
IND Clinical trials Discovering singledrug molecule and
further dev
US
$ m
illio
n
Global India
Indian Council of Medical Research
Cost savings by stage in India
70%45%40%
290260250
Drug Discoveryand Pre-Clinical
Clinical Trials Others
R&D spend/NDA in USD million
TOTAL USD 800 Million
SAVING USD 400 Million
Indian Council of Medical Research
Drugs Patents Filed in IPO1995-2001
433 465
8641089
1550
1015
1729
0200400600800
100012001400160018002000
1995 1996 1997 1998 1999 2000 2001
No.
of p
aten
ts fi
led
Annual Report, Deptt S&T, Min S&T, Govt of India, 2002-03
Indian Council of Medical Research
Drugs in Pipe-line
2853 31023278
5387
0
1000
2000
3000
4000
5000
6000
No.
of d
rugs
1996 1997 1998 2002
>250 clinical trials in progress, 2003
Indian Council of Medical Research
“India promises to become a world center for testing new medicines”
The Economist, London, 29th January 2000
“India can capture approx $1.0 billion worth of global clinical research spending by 2010”
“India can capture approx $1.0 billion worth of global clinical research spending by 2010”
McKinsey 2002
“Today India is identified as a major resource center for conducting clinical trials and data management services” -
Applied Clinical Trials, February 2003’
Indian Council of Medical Research
Indian Industries Engaged in New Drug Discovery
Ranbaxy (Malaria)Dr. Reddy’s Research FoundationLupin (TB)Astra Zeneca (TB)Zydus CadillaWochardtOrchidGlenmark
Indian Council of Medical Research
Goals to be achieved by 2000-2015
2010Reduce IMR to 30/100 and MMR to 100/lakh
2010Reduce Mortality by 50% on account of TB, Malaria and other vector and water borne diseases
2007Achieve Zero level growth of HIV/AIDS2015Eliminate Lymphatic Filariasis2010Eliminate Kala Azar2005Eliminate Leprosy2005Eradicate Polio and Yaws
Division of Epidemiology and Communicable Diseases
Role of Partners in HIV Vaccine Development
HIV/AIDSVaccine
IAVIMin Health & F W
ICMR
Design, develop and evaluate candidate vaccines appropriate for India
Capacity building, advocacy, training for vaccine trials
Transfer of technology for manufacture of vaccine in India
Facilitate permissions and permitsHarmonization of goals
Selection of Indian manufacturer
Select appropriate HIV strainProvide technical expertise
Collaborate in pre-clinical trials Cohort developmentCommunity preparednessConduct clinical trials
NACO
Division of Epidemiology and Communicable Diseases
Objective
Participate in development of one or more AIDS vaccine programmes aimed at developing safe and effective AIDS vaccine(s) suitable for IndiaForesaw IPR issues and that of access and equityStarted with MVA based vaccine
Division of Epidemiology and Communicable Diseases
Types of agreements
Overall project agreement between ICMR (GOI) and IAVIPatent and technology transfer agreement between ICMR and IAVIIPR and confidentiality agreement between ICMR and Therion Biologics
Division of Epidemiology and Communicable Diseases
Patent and IP Decisions
All new IP generated will be jointly held by IAVI and ICMRGOI shall have exclusive right to use all patent and other new IP rights to inventions arising out of the program in India and neighboring (SAARC) countries
Division of Epidemiology and Communicable Diseases
Patent and IP Decisions
ICMR grants non-excusive, world-wide, royalty-free, sub-licensable license to all new patent and other IP arising out of the project to permit IAVI or third parties selected by IAVI to make, use, sell offer for sale and import HIV/AIDS vaccine in countries other than those indicated in the agreement (to the extent ICMR has the right) to permit the use of the same
Division of Epidemiology and Communicable Diseases
Key lessons learnt
That only through strategic public-private partnership ventures as this can we succeed in providing effective and affordable vaccines to the peoplePrivate sector’s interests need to consideredRecognition of the crucial role of international NGOs like IAVI that can play the role of honest broker which is vital for the success of such projects
Division of Epidemiology and Communicable Diseases
Value addition to MVA
Indian scientist worked with US biotech firm TherionCompleted three constructs in MVA expression vectorsModified the MVA vector to accept 6 genes of India HIV strain C strainProto-type vaccine developed, undergoing pre-clinical toxicity studies
Division of Epidemiology and Communicable Diseases
Track-II
Simultaneously continued to scan HIV vaccine development around worldHave had top-level science reviews in India in which national experts met international researchers and evaluated other components
Division of Epidemiology and Communicable Diseases
Short-listed vaccines
VectorsAdeno Associated VirusAdeno 5Semliki Forest Virus
Division of Epidemiology and Communicable Diseases
Number of Microbicides under trial worldwide
Over 60 candidate Microbicide leads in the world20 tested in Phase I clinical trails3 in Phase II trails4 in Phase III effectiveness studies 6 Products shortly undergoing Phase III testing
Division of Epidemiology and Communicable Diseases
Number of Microbicides trials in India
Phase I studies on Buffer Gel, Pro 2000/5, Cellulose Sulphate
International collaboration with NIH, CONRAD and other agencies.Proposed Phase II studies with
Pro 2000/5, Buffer Gel and Polystyriene Sulphate (PSS)
Division of Epidemiology and Communicable Diseases
Indigenous Microbicides trials on Praneem Polyherbal
Patented in IndiaPhase I (safety) studies completed at NARIPhase II studies therapeutic against common RTIs completed through HRRCs.
Division of Epidemiology and Communicable Diseases
Agreement with Conrad
Signed in 2004Major components
Drug discovery and formulationPre clinical screeningPreparation of clinical sites to conduct Microbicide researchProvide opportunity for testing in India microbicides developed elsewhere; and tested Indian products elsewhere
Indian Council of Medical Research
Drugs for Visceral Leishmaniasis
Problems with existing drugsHigh costDifficulty in administeringDrug unresponsivenessToxicity
Indian Council of Medical Research
First effective oral remedy against VLSide-effects negligiblePhase-III success rates: 98%Simple chemical structureCan be produced in large quantities easilyEconomicalCan be stored indefinitely at 0-40 deg CCan control epidemic
Miltefosine
Miltefosine
Indian Council of Medical Research
Cure rate of VL after MILTEFOSINE in Relation to Prior Therapy
MILTEFOSINE - equally effective in newly diagnosed VL and those unresponsive to prior standard therapy
Final parasitological cure (ITT) missing/ n.a. no yes all
Treatment / Status of VL n % n % n % n
newly diagnosed 8 2.1 21 5.6 349 92.3 378Miltefosine previously treated 2 1.0 8 2.7 199 95.2 209
Miltefosine all patients 10 1.7 29 4.9 548 93.4 587newly diagnosed 1 1.4 0 0 70 98.6 71Ampho B previously treated 2 7.1 0 0 26 92.9 28
all patients 13 1.9 29 4.2 644 93.9 686
Integrated Analysis for VL
Indian Council of Medical Research
Going GlobalOutcome
Tackled IPR issuesStrengthened Public Private Partnership Led to the formulation of elimination programme by the GoI; but not inducted in ProgrammeGave a boost to development and evaluation of other anti-leishmaniasis drugs e.g. ParamomycinImproving regional access to the drug by including elimination of leishmaniasis for discussion during Ministers’ meeting at Regional ACHR meetingHas potentials for making global impact in countries which have leishmaniasis-HIV co-infectionNegotiating with other funding agencies (Bill & Melinda Gates)
Division of Epidemiology and Communicable Diseases
Causes of 1.5 million vaccineCauses of 1.5 million vaccine--preventable preventable deaths among children < 5 years, 2001deaths among children < 5 years, 2001
Diphtheria0.3%
Measles36.6%
Tetanus13.3%
Pertussis18.8%
Hepatitis B0.2%
Yellow fever1.0%
Hib29.8%
Poliomyelitis0.0%
Source: WHO estimatesSource: WHO estimates
Division of Epidemiology and Communicable Diseases
Current vaccine is excellent!
Over 40 years since it was licensedExcellent safety recordProved effectiveness when recommended strategies are implementedGood stability before reconstitutionLow cost
Approx US$ 0.26 (vaccine and safety equipment)
Division of Epidemiology and Communicable Diseases
Why do we need a Why do we need a new delivery system ?new delivery system ?
EASIER ADMINISTRATIONEASIER ADMINISTRATIONTo facilitate the administration, thus reducing the challenges of reaching every child
SAFETY CONCERNSSAFETY CONCERNSTo further address issues related to safe administration and reduce the burden of ensuring safe disposal of used sharps
SUPPLY AND POTENTIAL COST SAVINGSSUPPLY AND POTENTIAL COST SAVINGSTo help ensure sufficient vaccine supply and benefit from potential reductions in the cost per child vaccinated
Demand and availability of MCV to UNICEF, 1995-2003
0
50
100
150
200
250
300
350
400
1995 1996 1997 1998 1999 2000 2001 2002 2003
Mill
ion
dose
s
Availability
Demand
Division of Epidemiology and Communicable Diseases
no serious AEFIs, fewer than SC route
induced >80% response among infants < 9 months of age86-100% response in studies (1961-2002) among > 9 months & school-aged childrengood response with rubella vaccinegood response with rubella vaccine
lower attack rate (outbreak Mexico 1988-90):- immunized with aerosol (0.8%)(0.8%)- immunized with s-c (14%)(14%)- unvaccinated group (26%)(26%)
Measles aerosol immunizationMeasles aerosol immunization
SAFESAFE
IMMUNOGENICIMMUNOGENIC
EFFECTIVEEFFECTIVE
Division of Epidemiology and Communicable Diseases
Ultrasonic Ultrasonic nebulizersnebulizersCDC-Creare
Nasal spray systemsNasal spray systems
Current optionsCurrent options
Jet Jet nebulizersnebulizers
Mexico-INSP
Division of Epidemiology and Communicable Diseases
Investigational New Drugs
2002-0413 compounds screened
Antimicrobial agents: 3Migraine: 1Anti-hyperglycaemic agents: 2Urinary system 2Psoriasis 1Anti-ulcer drug 1Anti-histaminic agent 1Others 2
Division of Epidemiology and Communicable Diseases
Facilitating Clinical Trials
Currently available preparations for clot management: streptokinase, urokinase, tissue plasminogen activator, anistreplase, reteplaseThrombinase acts via different pathway; directly acts on fibrin without involving plasminogenFaster dissolution of blood clot and restoration of blood flowPatented in US and India