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?
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
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
DNDi’sFounding Partners Medecins Sans Frontieres WHO/TDR (permanent observer) Institut Pasteur, France Malaysian Ministry of Health Oswaldo Cruz Foundation, Brazil Indian Council for Medical Research Kenya Medical Research Institute
DNDi structure • Board of Directors • Scientific Advisory Committee • Coordinating/Executive team • Project Managers • Regional Liaisons • Financial & Administration Officers • Advocacy & Fundraising Officers
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?
World Pharmaceutical Market, 2002 SE Asia + China Rest of the world North America Latin America Japan EU Total $406 billion Source: IMS Health
Tropical diseases: 13 Tuberculosis: 3 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
Neglected diseases attract negligible R&D • A significant medical need exists, but : • These diseasesare 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
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.
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?
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 awarenessabout the need for R&D for neglected diseases • Use DNDi projects to strengthen existing capacityin disease-endemic countries.
Pre Clinical Development Availability to patients Discovery New chemical or bio-chemical compounds Fixed dose combinations;New indications of existing drugs Completing registration dossier;Reformulation Long-term projects Medium-term projects Short-term projects GAP3 GAP1 GAP2 DNDi’s portfolio will fill R&D gaps
Give top priority to patients’ needs Use innovative development models Adhere to international standards for drug development and registration Build regional networks DNDi’s approach
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?
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 Business Plan projections
Funding projection (USD million) Public Funding Private Funding Founding Partners
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)
Pre Clinical Development Availability to patients Discovery DNDi projects 2005 Target validation of dihydrofolate reductase for leish & tryps Combination therapy for VL Nifurtimox - Eflornithine for HAT Protease inhibitor for Chagas Artesunate-Amodiaquine for malaria Whole cell African trypanosome screen Trypanothione reductase inhibitors for leish + tryps Artesunate-Mefloquine for malaria Protein farnesyl-transferase inhibitors for trypanosomes Paromomycin for VL in Africa Protease inhibitors for HAT Imiquimod for cutaneous leish Nitro comps for HAT Benzofuroxan comps for Chagas disease HAT: Human African trypanosomiasis VL: Visceral leishmaniasis Leish: Leishmaniasis Tryp: Trypanosomiasis Ascofuranone for HAT
Capacity building • Identify new scientific partners • Tap existing research facilities and scientific knowledge • Transfer technology and strengthen existing capacity in developing countries
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
Leishmania East Africa Platform (LEAP) 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
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)
LEAP’s inaugural project Paromomycinfor 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
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 -notnecessary for KEMRI studies
GCP training 2004 Investigators inEthiopia, Kenya, Sudan TDR-WHO Monitors Clinical Trial Consulting, Basel DSMB Drug Research & Safety Unit, London
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
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
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