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Human African Trypanosomiasis Translation

  • Target disease: HAT
  • Partners (since project start): Anacor Pharmaceuticals Inc., USA; SCYNEXIS Inc., USA; Advinus Therapeutics, India; Penn Pharma, UK; BaseCon, Denmark; Optimed, France; PhinC, France; Cardiabase, France; SGS Cephac, France; Patheon, UK
  • Leadership: Discovery and Pre-clinical Director: Robert Don; Head of HAT Clinical Programme: Antoine Tarral; Clinical Manager: Sophie Delhomme; Head of Pharmaceutical Development: Steve Robinson; Project Coordinators: Delphine Launay, Beatrice Bonnet
  • Project start: January 2010
  • Funding (since project start): Bill & Melinda Gates Foundation, USA; Department for International Development (DFID), UK; Dutch Ministry of Foreign Affairs (DGIS), the Netherlands; Federal Ministry of Education and Research (BMBF through KfW), Germany; Médecins Sans Frontières/Doctors without Borders, International; Norwegian Government, Norway; Spanish Agency for International Development Cooperation (AECID), Spain; Swiss Agency for Development and Cooperation (SDC), Switzerland; BBVA Foundation, Spain; Other private foundations and individuals.

  • Progress SCYX-7158 pre-clinical programme
  • Manufacture SCYX-7158 tablet formulation; evaluate paediatric formulations
  • Complete SCYX-7158 Phase I programme
  • IMPD preparation and study site preparation for pivotal efficacy study

SCYX-7158 belongs to a unique boron-based chemical class, the oxaboroles, which was originally provided by Anacor Pharmaceuticals (a biopharmaceutical company in Palo Alto, California, USA) and screened for activity against T. brucei at the University of California San Francisco. A unique collaboration between DNDi, Anacor Pharmaceutical, and SCYNEXIS (a drug discovery and development company based in Research Triangle Park, North Carolina, USA), within a consortium that also included Pace University (USA) and the Swiss Tropical and Public Health Institute, enabled the identification of SCYX-7158, selected as a promising pre-clinical candidate in late 2009. In pre-clinical studies, SCYX-7158 was shown to be safe and efficacious to treat stage 2 of the disease, as it is able to cross the blood-brain barrier. Pre-clinical development progressed successfully in 2010.

Batches of drug substance and drug product (capsules) were produced according to current good manufacturing practices (cGMP) and supplied for the Phase I clinical trial. In 2012, a robust tablet formulation was also developed in order to supply Phase II/III clinical trials, with manufacturing and release of clinical tablets (40 and 160 mg unit doses) completed in September 2013. The latter demonstrated comparable pharmacokinetics to capsules in a Phase I study and the formulation is considered suitable for future clinical studies.

A GLP (Good Laboratory Practice) reproductive toxicity package was initiated in 2013 and expected to be completed in 2014. A dose-finding experiment showed that the drug was not teratogenic up to 40 mg/kg/day.

Following clearance by the French Ethics Committee and Regulatory Authority, SCYX-7158 entered First-in-Human studies in March 2012 and became DNDi’s first entity resulting from lead optimization efforts to enter early clinical development. The Phase I study in healthy volunteers of sub-Saharan origin was temporarily halted in 2013 after the first dose of SCYX-7158 showed a longer than expected half-life in human plasma, triggering the need for additional studies in dogs. The study was re-started in the same year, testing single ascending doses of treatments. Safety profiling in additional cohorts is ongoing.

Last update: September 2014

Tags: HAT – Sleeping Sickness
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