Pivotal clinical trial to begin for first oral drug candidate specifically developed for sleeping sickness

Basel, Switzerland — 8 Sep 2015

Phase I study shows favourable safety profile and can be tested in patients
The Drugs for Neglected Diseases initiative (DNDi) has announced today at the 9th European Congress on Tropical Medicine and International Health (ECTMIH) in Basel, Switzerland, the successful completion of Phase I human clinical trials for SCYX-7158 (AN5568), the first oral drug candidate specifically developed from the earliest drug discovery stage to combat human African trypanosomiasis, or sleeping sickness, a deadly parasitic disease transmitted by the tsetse fly.

The Phase I study, conducted in France, assessed the safety, tolerability, pharmacokinetics and pharmacodynamics of SCYX-7158 after single oral ascending doses in 128 healthy human volunteers of sub-Saharan origin. It allowed for the therapeutic dose to be determined at 960 mg administered once as three tablets, with a favourable safety profile. As the drug has a long half-life (400 hours), the study was extended to ensure extensive safety monitoring of the healthy volunteers up to 210 days. This pharmacological finding has the advantage of translating into prolonged exposure with just one dose. These Phase I results confirm that the drug penetrates the brain, which is crucial to treat the late stage of the disease, where the parasite crosses the blood-brain barrier and kills patients if no treatment is given. Based on the results of this study, DNDi and partners plan to proceed to pivotal Phase IIb/III studies in 2016 at sites in the Democratic Republic of the Congo (DRC), where 90% of cases occur.

‘We are encouraged by the results of this important milestone for SCYX-7158, which is the fruit of collaboration and hard work of many partners’, said Dr Antoine Tarral, Head of the Human African Trypanosomiasis Clinical Programme, DNDi. ‘The motivation has been the drug candidate’s potential of becoming the first ever, oral-only, single-dose treatment for this deadly disease.’ SCYX-7158 was discovered by Anacor Pharmaceuticals, Inc. The compound was identified through DNDi’s lead optimization programme and successfully progressed through pre-clinical development in 2011.

‘We are particularly excited about SCYX-7158 because it is the first drug candidate to come from the early discovery efforts of our lead optimization programme’, said Dr Rob Don, Discovery & Pre-clinical Director, DNDi.

Sleeping sickness cases are decreasing but the disease remains persistent in remote, hard-to-reach areas of Africa. One of the major advancements in the treatment of the disease was the introduction of nifurtimox-eflornithine combination therapy (NECT) in 2009, developed by DNDi, Médecins Sans Frontières/Doctors Without Borders (MSF), and partners. NECT replaced an old, arsenic-based medicine, and today the vast majority of all late-stage sleeping sickness patients receive this combination as first-line treatment. Yet NECT still requires skilled staff in a hospital setting to administer the injections. Patients often travel days to get to health centres. Fexinidazole, administered for ten days with food, is currently being tested in clinical trials as an oral-only treatment that could treat all stages of the disease. SCYX-7158, if successful, would have the additional benefit of its unique single-dose, simple oral tablet administration. Recruitment for patient trials is targeted to begin in 2016 at remote sites in the DRC, where DNDi has been carrying out fexinidazole clinical trials.

Funding support for this project
Funding for this project, including lead optimization, pre-clinical, and Phase I, has been provided by Médecins Sans Frontières (MSF) / Doctors Without Borders, the Swiss Agency for Development and Cooperation, the UK Department for International Development (DFID), the Dutch Ministry of Foreign Affairs (DGIS), Germany’s Federal Ministry of Education and Research (BMBF) through KfW and part of the EDCTP 2 Programme supported by the European Union, the Norwegian Agency for Development Cooperation (NORAD), the Bill & Melinda Gates Foundation, the French Ministry for Europe and Foreign Affairs, the Spanish Agency of International Cooperation for Development (AECID). A total budget of EUR 27.1 million for the development of SCYX-7158 has been spent to date, including EUR 5 million for the Phase I trial.

About SCYX-7158
SCYX-7158 (AN5568) is a product of Anacor’s novel boron chemistry which has produced a number of compounds with efficacy against a range of fungal, inflammatory, and bacterial diseases. Realizing this technology could also be used for neglected diseases, Anacor, with the help of the Sandler Center for Drug Discovery of the University of California, San Francisco, screened its library of boron-based compounds for activity against the sleeping sickness parasites and identified an attractive lead series. In order to ensure further development of these compounds, Anacor approached DNDi, which was actively seeking compounds for its lead optimization programme. DNDi, Anacor, SCYNEXIS, and a consortium including Pace University and the Swiss Tropical and Public Health Institute then worked on the series of molecules in pre-clinical studies that resulted in the DNDi-led Phase I studies now completed.

About the Drugs for Neglected Diseases initiative (DNDi)
A not-for-profit research and development organization, DNDi works to deliver new treatments for neglected diseases, in particular leishmaniasis, human African trypanosomiasis, Chagas disease, specific filarial infections, paediatric HIV, mycetoma, and hepatitis C. Since its inception in 2003, DNDi has delivered six treatments: 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 established regional disease-specific platforms, which bring together partners in disease-endemic countries to strengthen existing clinical research capacity, as well as to build new capacity where necessary. www.dndi.org