The Drugs for Neglected Diseases initiative (DNDi) has received a EUR 2 Million Strategic Translation Award from the Wellcome Trust to develop the azole compound E1224, a promising drug to treat Chagas disease being tested in adult patients in Bolivia. The Award, the first that DNDi has received from the Wellcome Trust, will take the project to the end of Phase II clinical trials.
The E1224 compound is a pro-drug which converts to ravuconazole, leading to the drug’s improved absorption and bioavailability. Previously studied to treat fungal diseases, E1224 has potent in vivo and in vitro activity against T. cruzi, the parasite that causes Chagas disease. In 2009, DNDi joined forces with Eisai Co. Ltd. – the Japanese pharmaceutical company that discovered E1224 – to develop this new chemical entity for Chagas disease.
‘This contribution from the Wellcome Trust is a first for DNDi. It gives us vital support in the Phase II clinical trial for this much needed oral drug for adult patients with Chagas disease. In addition, it reinforces our Chagas partnership with Eisai’, said Dr Bernard Pécoul, Executive Director, DNDi.
The Phase II proof-of-concept study started in July 2011 in Cochabamba and Tarija, Bolivia, which carries the world’s largest Chagas disease burden. It is estimated that about 7% percent of Bolivia’s population is reportedly infected with the disease. The study, coordinated by DNDi and conducted by the Barcelona Centre for International Health Research (CRESIB), Spain, and Platform of Integral Care for Patients with Chagas Disease at Universidad Mayor San Simon and Universidad Autónoma Juan Misael Saracho, Bolivia, will evaluate the potential of E1224 as an oral, easy-to-use, safe, and affordable treatment for Chagas disease. In addition, it will explore the currently most promising biomarkers of therapeutic response in Chagas disease.
This randomized, multicenter, placebo-controlled, safety and efficacy study will evaluate three oral E1224 dosing regimens (high dose for 4 weeks and 8 weeks; low dose for 8 weeks) and benznidazole (5mg/kg/day). Recruitment for the study will include 230 adult patients with chronic indeterminate Chagas disease.
If E1224 progresses successfully through Phase III clinical trials, it could become one of the first new treatments for Chagas disease in 40 years. The only current treatment options – nifurtimox and benznidazole – are known to have serious limitations in adult chronic patients, from allergies to potentially serious peripheral and central nervous system reactions, and their efficacy diminishes the longer the patient has been infected. The need for a safer and more efficacious treatment for adult chronic Chagas disease patients remains dire.
About Chagas disease
Chagas disease is endemic in 21 countries across Latin America, where it kills more people than any other parasite-borne disease, including malaria. It currently infects approximately 8 million people, kills an estimated 12,000 per year, and places 100 million people at risk.
Chagas disease is a chronic, systemic, parasitic infection caused by the protozoan Trypanosoma cruzi. In 30-40% of cases, chronic Chagas disease will affect the heart and/or the digestive system. It is potentially fatal and a leading cause of heart failure, resulting in frequent and prolonged hospitalization, use of pacemakers and defibrillators, and heart transplants. The disease leaves tens of thousands of young, working-age adults in hospitals across Latin America, and causes over a billion USD in economic losses annually.
As a result of worldwide population flows, Chagas disease is no longer confined to the Americas, with patient numbers growing in non-endemic countries, such as the United States of America, Australia, Europe, and Japan.
The Drugs for Neglected Diseases initiative (DNDi) is a not-for-profit research and development organization working to deliver new treatments for neglected diseases, in particular sleeping sickness (human African trypanosomiasis), Chagas disease, leishmaniasis, specific helminth infections, malaria, and paediatric HIV. DNDi was established in 2003 by Médecins Sans Frontières/Doctors Without Borders (MSF), the Oswaldo Cruz Foundation (FIOCRUZ) of Brazil, the Indian Council of Medical Research (ICMR), the Kenya Medical Research Institute (KEMRI), the Ministry of Health of Malaysia, and the Pasteur Institute of France. The Special Programme for Tropical Disease Research (WHO/TDR) serves as permanent observer.
Since its inception in 2003, DNDi has delivered six new treatments for neglected patients: two fixed-dose antimalarials (ASAQ and ASMQ), nifurtimox-eflornithine combination therapy (NECT) for late-stage sleeping sickness, sodium stibogluconate and paromomycin (SSG&PM) combination therapy for visceral leishmaniasis in Africa, a set of combination therapies for visceral leishmaniasis in Asia, and a paediatric dosage form of benznidazole for Chagas disease.
DNDi has helped establish three clinical research platforms: Leishmaniasis East Africa Platform (LEAP) in Kenya, Ethiopia, Sudan, and Uganda; the HAT Platform based in the Democratic Republic of Congo (DRC) for sleeping sickness; and the Chagas Clinical Research Platform in Latin America. Strong regional networks such as these help strengthen research and treatment-implementation capacity in neglected disease-endemic countries.
About the Wellcome Trust
The Wellcome Trust is a global charitable foundation dedicated to achieving extraordinary improvements in human and animal health. It supports the brightest minds in biomedical research and the medical humanities. The Trust’s breadth of support includes public engagement, education and the application of research to improve health. It is independent of both political and commercial interests.
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