Financing and Coordination of R&D for neglected diseases: Challenges and opportunities

1. Financing and Coordination of R&D for neglected diseases:Challenges and opportunities Consultative Expert Working Group on Research and Development Open Forum 6 April 2011 WHO, Geneva Dr. Bernard Pécoul Executive Director, DNDi

2. A Fatal Imbalance • Tropical diseases (including malaria) and tuberculosis account for: • 12% of the global disease burden • Only 1.3% of new drugs developed (1975-2004) Tropical diseases: 18 new drugs (incl. 8 for malaria) 1.3% 21 new drugs for neglected diseases Tuberculosis: 3 new drugs 98.7% 1,535 new drugs for other diseases Source: Chirac P, Torreele E. Lancet. 2006 May 12; 1560-1561.

3. 8 Pipeline now begins to be filled 143 candidates ... and 39 diagnostic & vector control candidates 104 biopharmaceutical candidates in development... Diagnostics Pre Clinical 59 57% 26% Feasibility 7 14% Test Development Phase I 15 26% 7 22% Evaluation 6 Phase II 12 12% CD4 4% Demonstration 1 FIND 22% Phase III 10 10% Country Adoption IDRI 6 Drugs 2 Registration 2% Vaccines Vector control Microbicides 6% Launched 6 Early Stage IVCC In Development # candidates Notes: Includes products not funded by Gates Foundation. Biopharmaceutical candidates in development Include: IAVI, IPM, IVI, GATB, Aeras, MMV, MVI, MVP, PVS, DNDi, iOWH, PDVI, HHVI. Source: PDPs # candidates & Source from:

4. DNDiA patient needs driven & innovative R&D model • Deliver 6 - 8 new treatments by 2014 for sleeping sickness, Chagas disease, leishmaniasis and malaria • Establish a robust pipeline for future needs • Use and strengthen existing capacity in disease-endemic countries • 7 Founding Partners • Indian Council for Medical Research (ICMR) • Kenya Medical Research Institute (KEMRI) • Malaysian MOH • Oswaldo Cruz Foundation Brazil • Medecins Sans Frontieres (MSF) • Institut Pasteur France • WHO/TDR (permanent observer) 7 worldwide offices Japan USA India DRC Malaysia Geneva Coordination Team + consultants Kenya Brazil

5. a robust pipeline 6 to 8 new treatments by 2014 DNDi portfolio: €100m spent since 2003 Discovery Activities: - Compound mining - Chemical classes - Target-based - Screening HAT LO Consortium - Scynexis - Pace Univ. Nitroimidazole backup (HAT) Fexinidazole (HAT) ASAQ(Malaria) Fixed-Dose Artesunate/ Amodiaquine Oxaborole (HAT) Combination therapy (VL in Asia) Alternative formulations of Amphotericin B (VL) • Combination therapy(VL in Africa) • AmBisome® • Miltefosine ASMQ(Malaria) Fixed-Dose Artesunate/Mefloquine VL LO Consortium - Advinus - CDRI Nitroimidazole (VL) Combination therapy (VL in Latin America) Drug combination (Chagas) K777 (Chagas) Chagas LO Consortium - CDCO - Epichem - Murdoch Univ. - FUOP NECT (Stage 2 HAT) Nifurtimox - Eflornithine Co-Administration Paediatric benznidazole (Chagas) Exploratory Azoles E1224 & Biomarker (Chagas) Exploratory SSG&PMCombination therapy (VL in Africa ) Major Collaborators: - Sources for hit and lead compounds: GSK, Anacor, Merck, Pfizer, Novartis (GNF, NITD), TB Alliance,… - Screening Resources: Eskitis, Institut Pasteur Korea, Univ. Dundee,… - Reference screening centres: LSHTM, Swiss Tropical & Public Health, University of Antwerp

6. Average Cost to Develop One Drug – The Pharmaceutical Industry Data Based on this model, DNDi would have to raise billions to accomplish its goals. Through effective partnerships, we are able to bring the costs down. (in $ Million) *Source: PhRMA Pharmaceutical Industry Profiles 2007

7. How much will R&D cost for neglected diseases? SSG&PM Sodium Stibogluconate & Paromomycin Combination Therapy VL in Africa 2010 NECT Nifurtimox - Eflornithine Co-Administration Stage 2 HAT 2009 €100 million = ASMQ (Malaria) Fixed-Dose Artesunate/Mefloquine 2008 ASAQ (Malaria) Fixed-Dose Artesunate/ Amodiaquine 2007 + a robust pipeline €1 billion 1 drug = Pharma

8. Main policy challenges • Challenge 1: IP and open innovation • Challenge 2: Overcoming regulatory barriers • Challenge 3: sustainable financing and new incentives for R&D

9. Challenge1 Access to compound librairies • Quality compounds sourcing • Access to focused knowledge and data • => Accessing proprietary compounds to jumpstart discovery • DNDi agreements with pharmas, biotechs, PDPs: • Merck • Pfizer • GSK • sanofi-aventis • Anacor • TB Alliance • Others in negotiation….

10. Challenge1 Need for more open innovation and sharing of knowledge • Nitroimidazole compounds developed by TB Alliance showed great promise for leishmaniasis treatment • Grant DNDi royalty free license to develop new compounds • sharing of scientific expertise and specific knowledge • Synergy between two PDPs – collaboration to benefit patients • avoid duplication • saving costs • speeding up R&D process • stimulate innovation

11. Challenge1 Negotiating freedom to operate… paving the way for equitable access • Royalty-free sub-licensable licenses • Licenses for R&D and manufacture: world-wide • Licenses for distribution and sale: all endemic regions, without exclusion • Sales on the public sector: at cost plus (lowest sustainable price) • Sales on the private sector: possible margins but linked to partner’s financial contribution • Limited confidentiality: make freely available all information generated about the product during its development (publications, databases, etc.)

12. ASAQ An innovative unpatented anti-malarial FDC • Innovative partnership with sanofi-aventis • DNDi formulation out-licensed to s-a • WHO prequalified • Registered in 28 sub-Saharan countries + India • Public price: “at cost” • < US$1 for adult, US$0.50 for children • Over 80 million treatments distributed in Africa • Next step : • Transfer of technology to an additional African industrial partner © MSF

13. Challenge1 IP & open innovation: DNDi vision • Affordable treatment and equitable access to patients in need • Delinking the costs of R&D from the price of products • DNDi activities not financed by IP revenues • No partnership without overcoming IP barrier • Develop drugs as public goods, when possible • Disseminate the results of DNDi work • Encourage open publication of research data and technology transfer • Decisions regarding ownership of patents and licensing terms made on a case-by-case basis

14. Challenge2 Overcoming regulatory barriers • Majority of treatments submitted for approval in Africa: • first approved by EMA/US FDA, or • generic drugs • New Chemical Entities (NCEs), vaccines, combination treatments now being developed to respond to the specific needs in endemic countries • African regulatory agencies will have to perfom regulatory assessment of new treatments never evaluated before • How can this be achieved the most efficiently? Dr. Jannin, WHO JS

15. Need for new pathways for registering innovative drugs for Africa Challenge2 • Increased participation of endemic countries within existing mechanisms • Regional centres of excellence to support strengthening of African regulatory agencies

16. Challenge3 Sustainable financing & incentive for R&D • Combined PDP pipeline include 143 Candidates • BUT • Sustainable funding not secured for expensive clinical trials • New incentives needed to replenish pipelines with new compounds • Global framework needed to ensure public health & access oriented R&D

17. PUSH and PULL mechanisms for stimulating R&D on neglected diseases

18. Challenge3 Sustainable funding for product development and access Funding needed for large efficacy trials, manufacturing scale-up, registration, delivery, and access Model: UNITAID airline ticket tax Other indirect tax proposals: • European tax on financial transactions • Digital tax, mobile phone tax, etc Possible benefits • New sources of funds • Ensures predictability required for long-term planning clinical development • Stable & subsidized market through interaction with international financing organizations • Faster registration, adoption, and delivery through interaction with WHO & international procurement agencies

19. Challenge3 Pilot milestone prizes Would pay a substantial reward (≅ € 5-20M) for specific steps in the discovery process or for clinical drug candidates that meet specific criteria Possible benefits • Replenish pipeline by motivating new actors such as biotechs • Vehicle to engage endemic countries as partners • Pay only for success (unlike conventional push funding) • Incentive to collaborate with PDPs • IP management to ensure access Source of funds • Usual donors: OECD governments, Foundations • Endemic country governments

20. Need for a global framework for R&D coordination • Central role of WHO • defining priorities • treatment recommendations • Extension of Prequalification to NTD • Endemic countries involvement • R&D partners • new funders • Identifying needs • Access oriented IP management • delinking R&D costs from final price • Technology transfer to strengthen capacity • New products as Public goods