Financing and Coordination of R&D
for neglected diseases:
Challenges and opportunities
Consultative Expert Working Group on Research and Development
Open Forum
6 April 2011WHO, Geneva
Dr. Bernard PécoulExecutive Director, DNDi
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Source: Chirac P, Torreele E. Lancet. 2006 May 12; 1560-1561.
A Fatal Imbalance
Tropical diseases:18 new drugs(incl. 8 for malaria)
Tuberculosis: 3 new drugs
1.3% 21 new drugs for neglected
diseases98.7% 1,535 new drugs
for other diseases
(1975-2004)
Tropical diseases (including malaria) and tuberculosis account for:•12% of the global disease burden•Only 1.3% of new drugs developed
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0 2 4 6 8
7Feasibility
7TestDevelopment
6Evaluation
1Demonstration
6CountryAdoption
CD4
FIND
IDRI
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
4%
22%
26%
22%
104 biopharmaceutical candidates in development...
104 biopharmaceutical candidates in development...
... and 39 diagnostic & vector control candidates
... and 39 diagnostic & vector control candidates
0 20 40 60
59Pre Clinical
15Phase I
12Phase II
10Phase III
2Registration
6Launched
Drugs
Vaccines
Microbicides
# candidates
10%
12%
14%
57%
6%
2%
7
5
0 2 4 6 8
Early Stage
InDevelopment
IVCC
# candidates
Diagnostics
Vector control
26%
Source from:&
Pipeline now begins to be filled 143 candidates
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Brazil
India
KenyaMalaysia
USA
DRC
Japan
Geneva Coordination Team + consultants
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
DNDi A 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
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dDNDi portfolio: €100m spent since
2003
Exploratory
Alternative formulations of Amphotericin B (VL)
Drug combination (Chagas)
Oxaborole (HAT)
Nitroimidazole backup (HAT) Fexinidazole (HAT) ASAQ (Malaria)Fixed-Dose Artesunate/
Amodiaquine
ASMQ (Malaria)
Fixed-Dose Artesunate/Mefloquine
Combination therapy (VL in Asia)
Paediatric benznidazole (Chagas)
Azoles E1224 & Biomarker (Chagas)
Exploratory
Combination therapy (VL in Africa)• AmBisome®• Miltefosine
Combination therapy (VL in Latin America)
NECT(Stage 2 HAT) Nifurtimox - Eflornithine
Co-Administration
HAT LO Consortium- Scynexis - Pace Univ.
Chagas LO Consortium- CDCO- Epichem- Murdoch Univ.- FUOP
VL LO Consortium- Advinus- CDRI
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
Discovery Activities:- Compound mining- Chemical classes- Target-based- Screening
SSG&PMCombination
therapy (VL in Africa )
K777 (Chagas)
Nitroimidazole (VL)
a robust pipeline
6 to 8 new treatments
by 2014
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Drug – The Pharmaceutical Industry Data
(in $
Mill
ion)
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.
*Source: PhRMA Pharmaceutical Industry Profiles 2007
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How much will R&D cost for neglected diseases?
+ a robust pipeline€1
billion1 drug
€100 million
Pharma
=
SSG&PMSodium Stibogluconate & Paromomycin Combination Therapy VL in Africa
NECTNifurtimox - Eflornithine Co-AdministrationStage 2 HAT
ASAQ (Malaria)Fixed-Dose Artesunate/ Amodiaquine
ASMQ (Malaria)Fixed-Dose Artesunate/Mefloquine
2010
2009
2008
2007
=
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Main policy challenges
• Challenge 1: IP and open innovation
• Challenge 2: Overcoming regulatory barriers
• Challenge 3: sustainable financing and new incentives for R&D
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DNDi agreements with pharmas, biotechs, PDPs:
• Merck
• Pfizer
• GSK
• sanofi-aventis
• Anacor
• TB Alliance
• Others in negotiation….
• Quality compounds sourcing• Access to focused knowledge and data
=> Accessing proprietary compounds to jumpstart discovery
Access to compound librairiesChallenge 1
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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
Challenge 1
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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.)
Challenge 1
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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
ASAQ An innovative unpatented anti-malarial FDC
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• 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
IP & open innovation: DNDi vision
Challenge 1
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JS Dr. Jannin, WHO
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?
Challenge 2
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Need for new pathways for registering innovative drugs for
Africa• Increased participation
of endemic countries within existing mechanisms
• Regional centres of excellence to support strengthening of African regulatory agencies
Challenge 2
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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
Challenge 3
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dPUSH and PULL mechanisms for stimulating R&D on neglected
diseases
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Sustainable funding for product development and access
Funding needed for large efficacy trials, manufacturing scale-up, registration, delivery, and access
Model: UNITAID airline ticket taxOther 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
Challenge 3
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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
Challenge 3
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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