Jaderson Lima, MD On behalf of François Bompart, MD

Transcription

1 Challenges and Successes of the FACT Project through Innovative Partnerships for the Development of Artesunate Combination Therapies for Malaria 5º. ENIFarMed São Paulo Brazil August 2011 Public-private partnerships for ASAQ development and field implementation Fighting Malaria. Jaderson Lima, MD On behalf of François Bompart, MD Sanofi Aventis, Access to Medicines

2 DNDi and Sanofi Aventis partnership for ASAQ Background: High efficacy of artesunate-based combinations (ACT) WHO (2001): recommended combination to slow down spread of drug resistance. 2002: DNDi started the FACT project; Sanofi: replacing its co-blister to a FDC (artesunate amodiaquine). In Dec 2004, agreement between DNDi and Sanofi Aventis on ASAQ «No profit, no loss» public price: target US$ 1 per treatment/adult No patents taken 2006: WHO preference for ACT over non-fixed dose options Continued collaboration in implementation and post-registration

3 ASAQ Winthrop key features ASAQ Winthrop : informal name for Coarsucam and Artesunate Amodiaquine Winthrop Adapted to patients needs Optimized AS/AQ ratio, to avoid over and under-dosage 4 dosages by age or weight range Simple dosing regimen Soluble tablets 36 months shelf-life WHO prequalified 2008

4 4 dosages, by age and weight range INFANTS 4.5kg to <9 kg 2-11 months TODDLERS 9kg to <18kg 1 to 5 years CHILDREN 18kg to <36kg 6 to 13 years ADOLESCENTS ADULTS 36kg 14 years and above

5 Tiered-pricing policy to ensure sustainable accessibility to the poorest patients Artesunate-Amodiaquine Winthrop Public markets: preferential price, including no profit-no loss prices < $1 for adults, <0.50 for children Coarsucam Private markets $2-3 wholesalers price

6 ASAQ Winthrop Status update

7 Available comparative clinical trial data (1) Versus loose AS+AQ: Burkina Faso: 750 children < 5 years and > 5kg 375 ASAQ Versus AQ: India: 300 adults and children 202 ASAQ Versus AL: Senegal, Mali, Cameroon, Madagascar: 941 adults + children >10 kg 628 ASAQ Benin: 225 children <10 years 90 ASAQ Liberia: 300 children < 5 years 150 ASAQ Liberia: 1000 patients > 5 years 498 ASAQ Senegal cohort study: 400 adults and children 200 ASAQ Colombia: 210 adults 105 ASAQ 8 studies, 3526 patients, 2248 treated with ASAQ Winthrop

8 Available comparative clinical trial data (2) Day 28 efficacy rates > 95 %, including in children < 5 years of age Safety profile similar to AL (Arthemether + Lumefantrine). Transient increases in liver transaminases Asymptomatic, reversible neutropenia Occasional transient rashes Nausea, vomiting, exceptionally leading to treatment discontinuation Registration status: (October 2010) 30 sub-saharan African countries

9 Delivery status (July 2010) 21 countries 2008: 6 million treatments 2009: 25 million treatments July million delivered 100 million expected by end 2011 Global Fund Direct country purchase Global Fund, World Bank and/or PMI

10 ASAQ Winthrop Pending issues : Risk Management Plan

11 ASAQ Winthrop Risk Management Plan Rationale Counterfeits and substandard versions will soon follow ASAQ launch : safety issues, rumors, controversies Available data from clinical studies have limitations: Patients numbers Controlled conditions Single malaria episodes Limited pharmacovigilance systems in sub-saharan Africa Coartem (Arthemeter + Lumefantrine) Oct 1998 Aug 2008 > 200 million treatments 137 spontaneous reports, 60% from Africa* No pharmacovigilance data from industrialized countries for malaria drugs * Dec 3, 2008 FDA Advisory Commitee Meeting, Bethesda, MD

12 WHO Department of Medicines Policy and Standards ASAQ Winthrop Risk Management Plan Table of Contents (1) 1. Identified risks: to be minimized with specific information Intake during first trimester of pregnancy Allergy 2. Potential risks: to be quantified in large-scale studies Hepatotoxicity Neutropenia / agranulocytosis Somnolence Audiometric dysfunction Extra-pyramidal symptoms Decreased efficacy (parasite resistance)

13 WHO Department of Medicines Policy and Standards ASAQ Winthrop Risk Management Plan Table of Contents (2) 3. Missing information: to be documented in new studies Safety of repeated administrations Specific populations (HIV/AIDS patients ) Second and third trimester of pregnancy Safety profile in non parasitaemic patients Drug interactions & Interactions with traditional drugs and remedies Efficacy in species other than P. falciparum

14 ASAQ Winthrop Risk Management Plan Key Features - Variety of study designs to address multiple safety issues and information gaps - Variety of study settings to address different malaria transmission patterns - 1st Risk Management Plan submitted to the WHO - 1st Risk Management Plan entirely set up in Africa - Complements and reinforces normal pharmacovigilance activities

15 ASAQ Winthrop Risk Management Plan Methods 1. Randomized comparative clinical trials > 5 2. Randomized comparative cohorts 2 3. Large-scale safety study 1 4. Field monitoring programme 1

16 ASAQ Winthrop Risk Management Plan Recent achievements Two completed clinical cohort studies: ASAQ vs AL repeated administrations over 2 years Senegal: 366 children and adults, 496 malaria episodes. Uganda: 413 children, 6033 malaria episodes: Field monitoring programme initiated in Côte d Ivoire, supported by MMV 4 study sites, 15,000 malaria episodes expected Evaluation of 4 artemisinin-based combinations in uncomplicated malaria in African children completed ( 4ABC Study, Dr U. d Alessandro, MMV, EDCTP)

17 ASAQ Winthrop Risk Management Plan Expected database Comparative clinical trials: > 2800 ASAQ patients Comparative cohort studies : 400 ASAQ patients x n malaria attacks (arthemether+lumefantrine) Field monitoring programme ~ 15,000 ASAQ-treated malaria attacks (community healthcare workers) real-life safety and effectiveness TOTAL ~ 20,000 case reports

18 How can partnerships improve access to ACTs?

19 How can we improve access to ACTs? Development: ACTs with - simple dosing regimen - adapted to children needs - suitable for community-based management Affordability: apply sustainable pricing policy that ensures ACT access to poorest patients. Ongoing monitoring of efficacy and safety: critical importance of continued postlaunch monitoring of efficacy and safety in the field. Information and Education: for appropriate use of ACTs and comprehensive disease management.

20 Sanofi aventis tools and services for comprehensive malaria management For health care professionals: medical information on diagnosis and treatment of malaria For communities and families : information on Prevention of malaria Management of suspected malaria cases Tool Box to be adapted by local stakeholders

21 Tools and services for comprehensive malaria management National hospitals Regional hospitals Physicians-GPs Nurses District hospitals Primary care centers Healthcare technicians Community centers Communities and families

22 Expanding partnerships for ASAQ Winthrop DNDi & Sanofi Aventis : development, registration, distribution MMV (Medicines for Malaria Venture): Risk Management Plan National Malaria Control Programmes : ACT distribution, information and education on malaria and appropriate use of ACTs Government agencies: pharmacovigilance, ACT procurement Funding organizations: ACT procurement Clinical investigators & scientists : data on ACT efficacy and safety WWARN (Worldwide Antimalarial Resistance Network): ACT resistance monitoring Research & Development partnerships to meet future challenges, especially resistance to artemisinin derivatives

23 Conclusion Access to Medicines for neglected diseases: greatly improved through partnerships. Public-Private-Partnership can be an effective way in developing countries. Distinct entities with different missions and objectives work together. DNDi-Sanofi proved to be a successfull partnership to fight malaria in dev. countries Acknowledgments THANK YOU!

24 Acknowledgements

25 Sanofi and DNDi - Drugs for Neglected Diseases initiative - Sign an Innovative Agreement to Generate New Drugs for Neglected Tropical Diseases [Paris, France and Geneva, Switzerland - May 30, 2011] Sanofi and Drugs for Neglected Diseases initiative (DNDi) : signed a three-year research collaboration agreement for the research of new treatments for nine neglected tropical diseases (NTDs), listed by the World Health Organization (WHO) for which new, adapted, and efficient tools are urgently needed to treat patients in endemic countries. This agreement is built upon a history of successful collaboration between Sanofi and DNDi Neglected Tropical Diseases covered by the agreement: This agreement covers nine neglected tropical diseases (NTDs): kinetoplastid diseases (leishmaniases, Chagas disease, and human African trypanosomiasis), helminth infections (lymphatic filariasis, onchocerciasis, and soil-transmitted helminthiasis), and dracunculiasis, fascioliasis, and schistosomiasis. Sanofi s involvement in neglected disease Since the 1940s, through research programmes and manufacturing of treatments for sleeping sickness and leishmaniasis. In 2001, Sanofi partnering WHO :sleeping sickness. In 2006: agreement to fight leishmaniasis, Buruli ulcer, and Chagas disease and renewed for a further 5 years in Challenges:Sanofi created in 2010, within Research & Development organization, a Therapeutic Strategic Unit : new anti-infectives. infectives. multiresistant bacterial infections as well as some NTDs.

26 ASAQ Winthop Infant (4.5-8 kg) (2 to 11 months) 25mg/67.5mg Toddler (9-17 kg) (1 to 5 years old) 50mg/135mg Child (18-35 kg) (6 to 13 years old) 100mg/270mg Adult ( 36 kg) 14 years old and above 200mg/540mg

27 Registration status (October 2010) 30 sub-saharan African countries ASAQ & Coarsucam registered Marketing authorisation granted

28 European Medicines Agency (EMA) Risk Management Plans Key sections 1. Identified risks 2. Potential risks 3. Missing information

29 ASAQ Winthrop clinical study sites in Africa