DNDi Briefing
Dr Catherine Royce
Senior Project Manager, DNDi Geneva
6th Global Forum on Bioethics in Research
Blantyre, Malawi
17 March 2005
Contents
DNDi’s origin, vision, and
Founding Partners
• What are neglected diseases?
Why are we interested in them?
• What are DNDi’s objectives?
How will we achieve them?
• How will DNDi obtain funds to
cover costs?
• Where are we today?
2
The DNDi idea
• Several NGOs and MSF raised the issue of access to
drugs amongst neglected populations in developing
countries
• DNDi established in July 2003 as a not for profit
organisation to meet the specific needs of these neglected
patients
• DNDi partners with experts in disease-endemic countries
in its work
3
DNDi’s Vision
•
Develop new drugs for people suffering
from neglected diseases
•
Ensure equitable access to new and
field- relevant health tools
•
Raise awareness of the need to develop
drugs for neglected diseases
•
Build public responsibility and
leadership in addressing needs of these
patients
4
DNDi’s Founding Partners
Medecins Sans
Frontieres
Institut
Pasteur,
France
WHO/TDR (permanent
observer)
Malaysian
Ministry of
Health
Oswaldo Cruz
Foundation, Brazil
Kenya Medical
Research
Institute
Indian Council for
Medical Research
5
DNDi structure
• Board of Directors
• Scientific Advisory Committee
• Coordinating/Executive team
– Project Managers
– Regional Liaisons
– Financial & Administration Officers
– Advocacy & Fundraising Officers
6
Contents
• DNDi’s origin, vision and
Founding Partners
What are neglected diseases?
Why are we interested in them?
• What are DNDi’s objectives?
How will we achieve them?
• How will DNDi obtain funds to
cover costs?
• Where are we today?
7
World Pharmaceutical Market, 2002
SE Asia +
China
Rest of the world
North
America
Latin
America
Japan
EU
Total $406 billion
8
Source: IMS Health
Only 1% of new drugs developed are
for neglected diseases
•
10/90 disequilibrium in health research spending
•
1975-1999: 1,393 new chemical entities marketed
•
68·7% registered products presented little or no therapeutic gain
Tropical diseases: 13
Tuberculosis: 3
9
Neglected diseases attract negligible
R&D
•
A significant medical need exists, but :
 These diseases are of no strategic (military,
security) interest
 Patients have
 No purchasing power
 No advocacy group to lobby for them
•
Thus there is no drug innovation for
neglected diseases
10
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)
GAP1
Discovery
mainly public sector
Pre
Clinical
Development
GAP2
Validated candidate drugs
do not enter clinical
development because of
strategic company
choices.
Availability
to patients
GAP3
New or existing drugs do not
reach patients: registration
problems, lack of production,
high prices, or not adapted to
the local conditions of use
11
Contents
• DNDi’s origin, vision and
Founding Partners
• What are neglected diseases?
Why are we interested in them?
What are DNDi’s objectives?
How will we achieve them?
• How will DNDi obtain funds to
cover costs?
• Where are we today?
12
DNDi’s objective to develop new
drugs is threefold
•
Develop a portfolio to address needs
 Short and medium-term projects making better
use of existing drugs
 Long-term projects that will identify new
compounds
•
•
Raise awareness about the need for R&D for neglected
diseases
Use DNDi projects to strengthen existing capacity in
disease-endemic countries.
13
DNDi’s portfolio will fill R&D gaps
New chemical or
bio-chemical
compounds
Long-term
projects
Fixed dose
combinations;
New indications of
existing drugs
Completing
registration
dossier;
Reformulation
Mediumterm
projects
Shortterm
projects
GAP1
Discovery
Pre
Clinical
Development
GAP2
Availability
to patients
GAP3
14
DNDi’s approach
1. Give top priority to patients’ needs
2. Use innovative development models
3. Adhere to international standards for
drug development and registration
4. Build regional networks
15
Contents
• DNDi’s origin, vision and
Founding Partners
• What are neglected diseases?
Why are we interested in them?
• What are DNDi’s objectives?
How will we achieve them?
How will DNDi obtain funds
to cover costs?
Where are we today?
16
Business Plan projections
•
US$255 million over 12 years to achieve
registration of 6 to 7 drugs and a balanced
portfolio of projects
•
Funding principle
– To obtain a mix of public and private funding
aiming to increase involvement and
responsibility of governments and international
organizations in R&D for neglected diseases
17
Funding projection
(USD million)
$25
Public Funding
$20
$15
Private Funding
$10
$5
Founding Partners
2012
2011
2010
2009
2008
2007
2006
2005
2004
$0
18
DNDi today
•
A mix of 9 short, medium and long-term
projects in 2004 portfolio
•
•
6 more projects selected for 2005 portfolio
Regional research network operational and
growing
– Kenya (Nairobi)
– Brazil (Rio de Janeiro)
– Malaysia (Penang)
– India (Delhi)
19
DNDi projects 2005
Discovery
Target validation of
dihydrofolate reductase
for leish & tryps
Whole cell African
trypanosome screen
Trypanothione reductase
inhibitors for leish + tryps
Protein farnesyltransferase inhibitors for
trypanosomes
Protease inhibitors for
HAT
Pre
Clinical
Development
Combination
therapy for VL
Nifurtimox Eflornithine for HAT
Protease inhibitor
for Chagas
ArtesunateAmodiaquine for
malaria
Availability
to patients
ArtesunateMefloquine for
malaria
Paromomycin for VL
in Africa
Imiquimod for
cutaneous leish
Nitro comps for HAT
Benzofuroxan comps for
Chagas disease
Ascofuranone for HAT
Ongoing
HAT: Human African trypanosomiasis
VL: Visceral leishmaniasis
Leish: Leishmaniasis
Tryp: Trypanosomiasis
2005
approved
projects
20
Capacity building
• Identify new scientific partners
• Tap existing research facilities and
•
scientific knowledge
Transfer technology and
strengthen existing capacity in
developing countries
21
DNDi rooted in networks
• DNDi is a “virtual” organisation based
•
•
on networks of scientists and scientific
institutions
DNDi founding partner institutions
have national and/or international
networks
DNDi projects also work with other
public and private organisations
22
Leishmania East Africa Platform (LEAP)
•University of Khartoum
•Federal Ministry of Health
•MSF- Holland
SUDAN
•Addis Ababa University
•DACA
•Ministry of Health
ETHIOPIA
+
DNDi
LEAP:
A group of scientists
and institutions
working on
developing clinical
trial capacity to
bring new
treatments to
patients
IOWH- India
IDA
WHO/TDR
•Ministry of Health
•KEMRI
KENYA
23
Role of LEAP
•
•
•
Facilitate clinical testing and
registration of new treatments for VL in
the region
Evaluate, validate and register
improved options that address regional
needs for leishmaniasis
Provide capacity strengthening for drug
evaluation and clinical studies in the
region (Ethiopia, Kenya and Sudan)
24
LEAP’s inaugural project
Paromomycin for Africa
• To register paromomycin (PM) as a new
alternative treatment for VL in East Africa
(Sudan, Ethiopia and Kenya)
• To confirm efficacy and safety of
paromomycin (and SSG)
• To confirm efficacy and safety of a shorter
combination course of PM/SSG
Clinical trials have begun in 5 east
African sites
25
Regulatory approval for trial
•
•
•
•
Institutional Ethics Committees
MSF International Ethics Committee
WHO-TDR Ethics Committee
National Authority in each country
-Sudan -Federal Ministry of Health
-Ethiopia -Drug Adminstration & Control Agency
-Kenya -not necessary for KEMRI studies
26
GCP training 2004
Investigators in Ethiopia, Kenya, Sudan
TDR-WHO
Monitors
Clinical Trial Consulting, Basel
DSMB
Drug Research & Safety Unit, London
27
Paromomycin project timetable
Trial Design phase: completed July 31st 2004
Trial Preparation phase: in progress
• approved in Sudan and Kenya
• in progress in Ethiopia, now expected early March ’05
• includes trial site needs assessment and facility
refurbishments/re-training e.g. new lab at Kassab
First site started recruitment 18th November ’04 –Sudan
Current status: 116 of 705 planned patients entered into
trial
28
Paromomycin project timetable contd.
Implementation phase
• Patient recruitment; 9-12 months
• Follow up six months
• Earliest finish date (last patient, last visit) end2Q06
Reporting phase
• Earliest data analysis and report end3Q06
• Earliest dossier submission end4Q06
• 2nd supportive, comparative trial vs amphotericin B
completion May 2005 by IOWH in India
29
LEAP 0104 trial design
• Multicentre, prospective, randomised, parallel group trial
1) SSG 30 days (20mg/kg/day) im injection
vs
2) PM 21 days (15mg/kg/day) im injection
vs
3) SSG/PM 17 days (dosages as above) im injection
• Primary end-point: 6 month cure rate
• Secondary end point: initial cure rate (test of cure at end of
treatment)
•
•
•
•
•
Sample size: n=705
Powered to show similarity in efficacy of all 3 regimens
Safety parameters; ECG, audiometry, LFTs, U&E, FBC
Good Clinical research Practice (pivotal for registration)
Data management and analysis by KEMRI
30