They need new drugs, vaccines and diagnosis now: reality of neglected diseases

1. They need new drugs, vaccines and diagnosis now: reality of neglected diseases Bernard Pecoul Executive Director, DNDi Geneva 7 December 2005

2. Global causes of death Infectious and parasitic diseases 19% Injuries 9% Respiratory 7% Perinatal 4.3% Infectious and Parasitic diseases 33% Maternal 1% Other non- communicable diseases 16.9% Cancers 12.5% Cardiovascular 29.3% Source: WHO Health Report 2004

3. Defining neglected diseases Global Diseases Most Neglected Diseases Neglected Diseases World pharmaceutical market> $518 bn in 2004

4. Sleeping sickness is a most neglected disease Source: WHO 2001 • An estimated 300,000 infected • 55 million at risk in sub-Saharan Africa • Difficult to diagnose • Fatal if untreated • Existing drugs: old - toxic - resistance - difficult to use - expensive

5. The needs remain huge Arsenical Anti-cancer drug

6. Leishmaniasis • An estimated 12 million people affected • Different forms: visceral, (muco)cutaeous, PKDL • 350 million people at risk in 88 countries • Per year: 1-1.5 million new cases of CL/MCL • 500,000 cases of VL • VL is fatal if left untreated • Existing drugs: old - toxic - resistance - difficult to use - expensive

7. Buruli ulcer Source: WHO, WHO/CDS/CPE/GBUI/2001.1

8. AIDS is a neglected diseasefor adults and children living in developing countries • Drugs not adapted to health systems of endemic countries • No treatment adapted to children • Limited tools for diagnosis and follow up • No field-adapted preventive tools

9. Treatments do not exist or are inadequate and inaccessible • Toxic • Expensive • Painful to deliver • Difficult to follow up • Not adapted to patient’s needs • Not registered in endemic regions • Restricted by patents

10. Analysing the problems: Fatal imbalance

11. Developing countries have a tiny share of the pharma market World Pharmaceutical Market, 2004:Total $518 billion Source: IMS Health

12. Tropical diseases: 13 Tuberculosis: 3 Only 1% of new drugs developed are for neglected diseases • Approx. 1-2% is spent on R&D for neglected diseases • 10/90 gap in health research spending • 1975-1999: 1,393 new chemical entities marketed

13. Spending on health R&D has increased • World-wide spending on health R&D was never so high • Estimated at US$106bn for 2004 (GFHR, 2004) • Since 90’s: private sector has become biggest investor US-spending on health R&D:(>2/3rd total) Sources: For government: National Science Foundation 2004, http://www.nsf.gov/sbe/srs/nsf04329/pdf/nsf04329.pdf For Industry: PhRMA 2004, http://www.nsf.gov/sbe/srs/nsf04329/pdf/nsf04329.pdf

14. Pre Clinical Development Availability to patients Discovery GAP2 GAP3 GAP1 Gaps exist in the R&D process for neglected diseases… New knowledge on drug targets and lead compounds is published but pre-clinical research does not begin mainly industry (in North) mainly public sector New or existing drugs do not reach patients: registration problems, lack of production, high prices, or not adapted to the local conditions of use Validated candidate drugs do not enter clinical development because of strategic company choices.

15. Drug development largely confined to the R&D-based pharmaceutical industry operating for profit Poorer patients are thus neglected …due to failure of the market and public policy Public policy failure Market failure • Public policy does not redress this imbalance

16. DNDi’s created in 2003: vision • Use an alternative model to develop new drugs for neglected diseases - leishmaniasis, sleeping sickness and malaria • Ensure equitable access of needs-driven products • Strengthen existing capacity in disease-endemic countries • Build public responsibility and leadership in addressing needs of these patients • Bring together the international community, public sector and pharmaceutical industry

17. DNDi’sFounding Partners Medecins Sans Frontieres (MSF) WHO/TDR (permanent observer) Institut Pasteur, France Malaysian Ministry of Health Oswaldo Cruz Foundation, Brazil Indian Council for Medical Research (ICMR) Kenya Medical Research Institute (KEMRI)

18. 18 projects in DNDi’s portfolio 2005

19. Discovery Nitroimidazoles project for trypanosomiasis OBJECTIVE: To identify new drug candidates amongst old and new nitroimidazoles for trypanosomiasis • sanofi-aventis, France-Germany • Roche, CH • Chiron, USA • Novartis (NITD), CH -Singapore • Romark, USA • Alkem, India Pharma • Swiss Tropical Institute • Fiocruz, Brazil • U of Sao Paolo, Brazil • U of Tehran, Iran • U of Bern, CH • Silesian University, Poland • Roma University, Italy • + contacts Japan, USA Academics DNDi • TB alliance • Dr Nagarajan , India other

20. Pre-clinical development Ravuconazole project for Chagas disease OBJECTIVE: To investigate the activity and toxicity of ravuconazole in preclinical disease models for acute and chronic Chagas disease Pharma companies Eisai, JAPAN Academic groups • Federal Univ of Ouro Preto, Brazil • Instituto Venezolano de Investigaciones Científicas, Venezuela DNDi

21. Clinical development Leishmaniasis East Africa Platform (LEAP) A group of scientists and institutions working on developing clinical trial capacity to bring new treatments to patients • University of Khartoum • Federal Ministry of Health • MSF- Holland SUDAN • Addis Ababa University • DACA • Ministry of Health ETHIOPIA DNDi IOWH- India IDA WHO/TDR • Ministry of Health • KEMRI KENYA

22. Agreement between DNDi and sanofi-aventis

23. Governments should tackle this imbalance • The response should not be purely philanthropic • Governments should increase public responsibility towards R&D of drugs for neglected diseases • More political leadership • Sustained financial support • New rules to stimulate drug R&D

24. Increased public responsibility:1. More public leadership • Make global health and medicines a strategic priority • Set R&D agenda according to the needs of patients

25. Increased public responsibility: 2. Sustained financial support Governments need to • Raise current levels of funding for neglected diseases by 3 billion euros per year to start to correct the 10/90 gap • Put in place new, sustainable funding mechanisms

26. 2. Sustained financial support This funding should be focused on: • A needs-driven R&D agenda for safe, effective, affordable and field-adapted treatments • Encouraging scientific community to do basic research on neglected diseases • Translation of basic research to new medical applications, e.g. by supporting PDPs • Encouraging R&D capacity strengthening in disease-endemic countries • Securing the market

27. Increased public responsibility: 3. New rules to stimulate drug R&D • Regulatory standards • Streamline regulatory approval processes to rapidly deliver essential medicines to patients • Analyse risks and benefits of each drug or vaccine in relation to the needs of patients, severity of the disease and lack of alternative solutions • Regulatory authorities (FDA and EMEA) should provide support and transfer know-how to authorities in developing countries

28. 3: New rules to stimulate drug R&D Intellectual Property: develop drugs as public goods • Guarantee that the public sector develops open access to information (recent Wellcome Trust policy) => open source (Human Genome Project) => freedom to operate • Ensure that industry provides sustainable access to knowledge, chemical compounds and tools • Make technology transfer happen to disease-endemic countries

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