Status: Fexinidazole, a drug candidate for stage 2 HAT, is the first success of the proactive compound mining efforts DNDi pursued in the Nitroimidazole Project. Fexinidazole was in pre-clinical development as a broad-spectrum antiprotozoal at Hoechst AG in the early 1980s, but was then abandoned. DNDi “rediscovered” it and an extensive profiling has shown that fexinidazole is orally active in animals, crosses to the brain in mice, and has cured in models for both acute and chronic infections with African trypanosomes. Additionally, fexinidazole is not mutagenic (i.e. is not capable of inducing mutation) in a panel of in vitro and in vivo mammalian genetic toxicology tests, confirming its favourable activity/toxicity profile as a drug candidate.

In 2007, a full pre-clinical programme was established to enable first-in-human studies. This included: process chemistry; GMP (good manufacturing practice) manufacturing of the active pharmaceutical ingredient; pre-clinical formulation; ADME-PK (absorption, distribution, metabolism, excretion, and pharmacokinetics) profiling and confirmatory studies in animal models of HAT; and the regulatory toxicology package. In May 2009, DNDi signed an agreement with sanofi-aventis (now: Sanofi),whereby DNDi is responsible for non-clinical, clinical, and pharmaceutical development, whereas sanofi-aventis is responsible for the industrial development, registration, and production of the drug at its manufacturing sites. Fexinidazole entered into Phase I first-in-human studies in September 2009, which makes it the only new drug candidate currently in clinical development for sleeping sickness. By the end of 2010, the three planned studies (single ascending dose, food effect, multiple ascending dose) had been completed. Additional studies are planned in 2011 in order to find the adequate regimen and treatment duration.
In 2010, DNDi and its partners submitted the protocol to the French ethical and regulatory authorities, for a new Phase I study assessing pharmacokinetic profile after administration with field food. Together with DNDi’s partner sanofi-aventis, a parallel scientific advice from EMA (under the article 58) and FDA on the clinical development plan of fexinidazole was requested and took place in 2010. Results of the consultation are expected in January 2011.