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%

Perinatal4.3%

Maternal1%

Cancers12.5% Cardiovascular

29.3%

Other non-communicable diseases 16.9%

Respiratory7%

Injuries9%

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

Sou

rce:

WH

O 2

001

Sou

rce:

WH

O 2

001

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: 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

Buruli ulcer

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

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

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

Rest of Europe $9bn (1.8%)

Japan $58bn (11.1%)

Latin America $19bn (3.8%)

Asia, Africa and Australia $40bn

(7.7%)

North America $248bn (47.8%)

EU $144bn (27.8%)

Developing countries have a tiny share of the pharma marketWorld 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

• 1975-1999: 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:(>2/3rd total)

Sources:For government: National Science Foundation 2004, http://www.nsf.gov/sbe/srs/nsf04329/pdf/nsf04329.pdfFor Industry: PhRMA 2004, http://www.nsf.gov/sbe/srs/nsf04329/pdf/nsf04329.pdf

0.0

5.0

10.0

15.0

20.0

25.0

30.0

35.0

1980 1985 1990 1995 2000 2005

Government

Industry

Bn US$

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)

Availabilityto patients

DevelopmentPre

ClinicalDiscovery

GAP2 GAP3

GAP1

…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

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

DNDi’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 DNDi’s portfolio 2005

oth

er DNDi

Nitroimidazoles project for trypanosomiasisA

cad

emic

sP

har

ma

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

DNDi

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

patientsETHIOPIA

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

DNDi

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

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