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
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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%
98.7%
Tuberculosis:
3 new drugs
21 new drugs
for neglected
diseases
1,535 new drugs
for other diseases
Source: Chirac P, Torreele E. Lancet. 2006 May 12; 1560-1561.
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Pipeline now begins to be filled
143 candidates
... and 39 diagnostic & vector control
candidates
104 biopharmaceutical candidates in
development...
Diagnostics
Pre Clinical
59
57%
Phase I
15
Phase II
14%
Feasibility
7 26%
Test
Development
7 26%
6 22%
Evaluation
12 12%
Demonstration
Phase III
10 10%
Drugs
Vaccines
Microbicides
6 6%
Launched
0
20
22%
6
Country
Adoption
2 2%
Registration
0
2
4
8
5
IVCC
In
Development
7
0
2
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
Source from:
6
Vector control
Early Stage
40
60
# candidates
CD4
FIND
IDRI
1 4%
&
4
6
8
# candidates
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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
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
Geneva Coordination
Team + consultants
USA
Japan
India
DRC
Malaysia
Kenya
Brazil
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DNDi portfolio: €100m spent since 2003
Discovery Activities:
- Compound mining
- Chemical classes
- Target-based
- Screening
a robust
pipeline
HAT LO
Consortium
- Scynexis
- Pace Univ.
VL LO
Consortium
- Advinus
- CDRI
Chagas LO
Consortium
- CDCO
- Epichem
- Murdoch
Univ.
- FUOP
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
Nitroimidazole backup (HAT)
Fexinidazole (HAT)
ASAQ (Malaria)
Oxaborole (HAT)
Combination therapy (VL in Asia)
Alternative formulations of
Amphotericin B (VL)
Fixed-Dose
Artesunate/
Amodiaquine
Nitroimidazole (VL)
Combination therapy (VL in Africa)
• AmBisome®
• Miltefosine
Drug combination (Chagas)
Combination therapy
(VL in Latin America)
K777 (Chagas)
Paediatric benznidazole (Chagas)
Exploratory
Azoles E1224
& Biomarker (Chagas)
Exploratory
ASMQ
(Malaria)
Fixed-Dose
Artesunate/
Mefloquine
NECT
(Stage 2 HAT)
Nifurtimox Eflornithine
CoAdministration
SSG&PM
Combination
therapy
(VL in Africa )
6 to 8 new
treatments
by 2014
(in $ Million)
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Average Cost to Develop One Drug –
The Pharmaceutical Industry Data
*Source: PhRMA Pharmaceutical Industry Profiles 2007
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.
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How much will R&D cost for
neglected diseases?
SSG&PM
Sodium Stibogluconate &
Paromomycin
Combination Therapy VL
in Africa
2010
NECT
€100 million
=
Nifurtimox - Eflornithine
Co-Administration
Stage 2 HAT
ASMQ (Malaria)
Fixed-Dose Artesunate/
Mefloquine
ASAQ
(Malaria)
Fixed-Dose Artesunate/
Amodiaquine
1 drug =
€1 billion
Pharma
+ a robust pipeline
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
Challenge 1
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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….
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Challenge 1
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
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Challenge 1
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.)
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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
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Challenge 1
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
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Challenge 2
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?
JS
Dr. Jannin, WHO
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Challenge 2
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
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Challenge 3
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
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PUSH and PULL mechanisms for
stimulating R&D on neglected diseases
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Challenge 3
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
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
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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