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