DNDi participated with presentations on the Leishmaniasis East Africa Platform and on Chagas disease, and also had several posters and a DNDi booth.
If you would like to download the Detailed Programme of DNDi attendance, please click here.
Presentations
“How regional platforms may facilitate innovation and access to new tools: The example of LEAP (Leishmaniasis East Africa) Platform” by Monique Wasunna, DNDi Africa/KEMRI
in the Symposium “A Decade Later: Drug Development and the Promise of Health Care Impact”
“Clinical trial of E1224 for treatment of Chagas disease” by Isabela Ribeiro, DNDi
in the Symposium “CYP51 as a Target for Chagas Disease Drugs”
Posters
“Analogues of fenarimol as novel compounds for the treatment of Chagas disease”
– AUTHORS: Martine Keenan [presenter],1 Mike Abbott,1 Paul Alexander,1 Tanya Armstrong,2 Wayne Best,1 Bradley Berven,1 Adriana Botero,2 Jason Chaplin,1 Susan Charman,3 Eric Chatelain,4 Hugo Diao,1 Tom von Geldern,4 Maria Kerfoot,2 Andrea Khong,2 Joshua McManus,1 Ivan Scandale,4 Andrew Thompson,2 Zhisen Wang,1 Karen White3
– AFFILIATIONS: 1. Epichem, Perth, Australia; 2. School of Veterinary & Biomedical Sciences, Murdoch University, Perth, Australia; 3. CDCO, Monash University, Melbourne, Australia; 4. Drugs for Neglected Diseases initiative, Geneva, Switzerland
“Flubendazole as a potential macrofilariacide for field use”
– AUTHORS: Charles MacKenzie,1 Timothy Geary,2 Nicole Madrill,1 Carlos Lanusse,3 Robert Don4
– AFFILIATIONS: 1. Michigan State University, East Lansing, MI, United States; 2. McGill University, Montreal, Canada; 3. Universidad Nacional del Centro, Tandil, Argentina; 4. Drugs for Neglected Diseases initiative, Geneva, Switzerland
“A systematic review and meta-analysis of non-randomized and randomized controlled studies of artesunate and amodiaquine for the treatment of uncomplicated falciparum malaria in Africa”
– AUTHORS: Piero L. Olliaro,1 Michel Vaillant,2 Michael O. Harhay3
– AFFILIATIONS: 1. World Health Organization (WHO), Geneva, Switzerland; 2. Santé, Luxembourg, Luxembourg; 3. University of Pennsylvania, Philadelphia, PA, United States
“Safety and effectiveness of meglumine antimoniate in the treatment of Ethiopian visceral leishmaniasis patients with and without HIV co-infection”
– AUTHORS: Zewdu H. Dadi,1 Workagegnehu Hailu,1 Teklu Weldegebreal,1 Hailemariam Tafes,2 Raymond Omollo,3 Sisay Yifru,1 Manica Balasegaram,4 Asrat Hailu5
– AFFILIATIONS: 1. University of Gondar, Gondar, Ethiopia; 2. Arbaminch Hospital, Arbaminch, Ethiopia; 3. Kenya Medical Research Institute (KEMRI), Nairobi, Kenya; 4. Drugs for Neglected Diseases initiative (DNDi), Geneva, Switzerland; 5. Addis Ababa University, Addis Ababa, Ethiopia
In sub-Saharan Africa, visceral leishmaniasis (VL) is treated with either PentostamTM (sodium antimony gluconate) or generic sodium stibogluconate (SSG), except in Uganda where Glucantime® (meglumine antimoniate) has been in use for at least a decade. Between January 2008 and February 2009, 54 Ethiopian VL patients were treated with Glucantime. The medical charts of these patients were reviewed to assess the effectiveness and safety profile of Glucantime in a routine healthcare setting. None of the patients from south Ethiopia (n=24) and 46.4% of the patients from north Ethiopia (n=30) were HIV co-infected. At completion of treatment (Day 31), cure rates were 78.6% (95% CI 59.0-91.7%) in north Ethiopia and 100% (95% CI 85.8-100%) in south Ethiopia. Thirty-three non-serious and six serious adverse events (two pancreatitis, one renal failure and three deaths) were observed in 26 patients. One-third of the non-serious adverse events were due to biochemical pancreatitis. During treatment, a case-fatality rate of 10.0% in north Ethiopia and 0.0% in south Ethiopia was noted. These data show that Glucantime can be as effective as Pentostam or SSG in HIV-negative patients. The data also point to clinical pancreatitis as a safety concern, especially in patients with HIV co-infection. “Plasmodium falciparum polymorphisms and human CYP2C8 polymorphisms in clinical efficacy of artemisinin-based combination therapies in Liberia”
– AUTHORS: Sabina Dahlstrom,1 Vincent Jullien,2 Oumou Maiga-Ascofare,1 Birgit Schramm,3 Joel J. Jones,4 Yah M. Zolia,4 Elizabeth A. Ashley,3 Jean-Rene Kiechel,5 Philippe J. Guerin,3 Jacques Le Bras,6 Sandrine Houze7
– AFFILIATIONS: 1. Institut de Medecine et d’Epidemiologie Appliquee, Paris, France; 2. Saint-Vincent de Paul hospital, AP-HP, Paris, France; 3. Epicentre, Paris, France; 4. National Malaria Control Programme, Ministry of Health and Social Welfare, Monrovia, Liberia; 5. Drugs for Neglected Diseases initiative, Geneva, Switzerland; 6. Paris-Descartes University, IRD UMR216, Paris, France; 7. Parasitology Laboratory French National Malaria Reference Centre, AP-HP, Bichat-C. Bernard Hospital, Paris, France
Efficacy of artemisinin-based combination therapy in the treatment of uncomplicated malaria remains high in Africa, although treatment failures are not rare in clinical trials and reinfections are abundant in regions of high endemicity. Our aim was to understand genetic factors contributing to occurrence of recurrent infections by; 1) studying the selection of P. falciparum polymorphisms in pfcrt, pfmdr1 and pfmrp1 in patients treated with artesunate-amodiaquine (ASAQ) or artemether-lumefantrine (AL) and 2) assessing whether malaria patients with polymorphisms in CYP2C8, the major enzyme in the metabolization of amodiaquine (AQ) to its active metabolite monodesethylamodiaquine (DEAQ), have lower blood concentration of DEAQ after ASAQ treatment. P. falciparum infected patients from a clinical efficacy trial comparing fixed dose ASAQ (n=150) with AL (n=150) and from the ASAQ arm (n=498) of a tolerability trial conducted in Saclepea Comprehensive Health Center in Nimba county, Liberia, were analysed. In the efficacy trial parasite molecular markers pfcrt K76T, pfmdr1 N86Y, Y184F, D1246Y and pfmrp1 I876V and K1466R were assessed in pre- and post-treatment blood samples. The three main polymorphisms of CYP2C8, *2, *3 and *4, were analysed in patients treated with ASAQ. Pfmdr1 1246Y was observed to be selected in reinfections in the ASAQ arm and pfcrt K76 and pfmdr1 N86 were selected in AL reinfections. Reinfections carrying pfmdr1 1246Y and pfmdr1 N86 was observed to occur early, in the ASAQ and the AL arm respectively. A substantial prevalence of CYP2C8*2 (29%) was observed, whereas the *4 and *3 polymorphisms were detected rarely or not at all. In the efficacy trial patients with CYP2C8*2 polymorphisms had a slightly lower, concentration of DEAQ at day 7, however not reaching statistical significance. This trend was not seen in the tolerability trial. CYP2C8*2 was not a significant risk factor for treatment failure or reinfection after ASAQ treatment. Selection of reinfecting parasites may indicate tolerance, a first step in the process towards full drug resistance.
Blog
Anatomy of projects: PDP lessons
December 6, 2011
By John Donnelly
A decade ago, many global health experts trying to develop new drugs, vaccines, or diagnostic tools admitted they had a market failure. Industry dropped projects because they couldn’t be assured of making a profit. Researching solutions for diseases affecting mainly the poor started to dry up.
The crisis led to the formation of several groups called Product Development Partnerships, or PDPs. They were tasked to hunt for promising research, possible players, and funders, under the theory that together the actors could produce a breakthrough unattainable to a group working alone.
In a session Tuesday at the ASTMH annual meeting in Philadelphia, representatives from PDPs; biotech and pharmaceutical companies; NGOs; and the World Health Organization talked about successes from the collaborations – as well as suggestions on ways to improve the model.
Dr. Robert D. Newman, director of Global Malaria Programme at WHO, said that PDPs such as Medicines for Malaria Venture (MMV), the Foundation for Innovative New Diagnostics, and the Malaria Vaccine Initiative have been invaluable. “From the seat I sit in, there is an array of PDPs that have been essential to the progress we have made and we will need in the future,” he said.
He said it was urgent to produce new malaria drugs given the findings of resistance to artemisinin along the Cambodia-Thailand border, a development that malaria experts believe is likely the start of an eventual spread of resistance around the world.
“We need to be working on new medicines,” Newman said. “But without PDPs, we would not have this pipeline (for drugs and vaccines) we have in place today.”
Two representatives of industry — Dr. Yves Ribeill, CEO of SCYNEXIS, a Durham, N.C.-based biotech firm, and Silvio C. Gabriel, executive vice president and head of Malaria Initiatives at Novartis Pharma – said their PDP experiences were fruitful but they also suggested improvements.
Both teamed with multiple partners – SCYNEXIS on a drug candidate for Human African Trypanosomiasis, or sleeping sickness, and Novartis on several malaria drugs, including a pediatric formulation.
Ribeill said that 50 percent of new drugs for neglected diseases were the result of biotech innovation and “if we want to make a greater impact, biotechs can play a very strong role.”
The sleeping sickness project, which was managed by Drugs for Neglected Diseases initiative, needed many pieces to come together, he said. It required $15 million in funding over three years; a partner, Anacor, to provide technology due to a “very motivated CEO;” and his motivation and those of scientists at SCYNEXIS, including “some who asked not to be taken off the project and if they had to leave it, they said they were willing to work for free.” In all, he said, 19 people were working on the project, which has produced a drug candidate that will enter clinical trials next year.
Novartis’ Gabriel said pharmaceutical companies needed to make clear-eyed assessments about the economics of a project as well as how it would affect the company reputation. In the end, his collaboration with MMV and others produced more than 400 million treatments of malaria medication. That was his bottom line, he said, but he added that Novartis did not make money on the venture and at the beginning it absorbed a reputational hit when Doctors Without Borders led a protest that Novartis was not producing more malaria drugs.
The truth, he said, was that it took 14 months to produce the drugs from the manufacturer, and Novartis was given a 12-month deadline. Other issues, he said, was the poor forecasting on the need for malaria drugs. In 2005, for instance, Novartis was asked to produce 30 million treatments but only 9 million were used.
His lessons: the project should plan not just research and development but also include what is best for the patient; support from a company CEO was essential; partners need to share the same values; all have to contribute; and a “great team is needed.”
“For me, this was the most fascinating job I ever did,” Gabriel said. “For my personal life, this was the best experience I ever had.”
