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

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

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

Sleeping sickness is a most neglected disease 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 Source: WHO 2001

The needs remain huge Arsenical Anti-cancer drug

Leishmaniasis An estimated 12 million people affected  Different forms: visceral, (muco)cutaeous, PKDL 350 million people at risk in 88 countries Per year: 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

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

AIDS is a neglected disease for 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

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

Analysing the problems: Fatal imbalance

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

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

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: (>2/3 rd total) Sources: For government: National Science Foundation 2004, For Industry: PhRMA 2004, Spending on health R&D has increased

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 Validated candidate drugs do not enter clinical development because of strategic company choices. New or existing drugs do not reach patients: registration problems, lack of production, high prices, or not adapted to the local conditions of use mainly public sector mainly industry (in North) Availability to patients Development Pre Clinical Discovery GAP2GAP3GAP1

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

DND i ’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

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

18 projects in DND i’ s portfolio 2005

other DND i Nitroimidazoles project for trypanosomiasis Academics Pharma OBJECTIVE: To identify new drug candidates amongst old and new nitroimidazoles for trypanosomiasis 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 sanofi-aventis, France-Germany Roche, CH Chiron, USA Novartis (NITD), CH - Singapore Romark, USA Alkem, India TB alliance Dr Nagarajan, India Discovery

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

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

Agreement between DNDi and sanofi-aventis

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

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

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

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

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

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