BIA 10-2474: 6 volunteers in a French trial, 1 dead, 5 with brain damage

BIA 10-2474 was an experimental FAAH inhibitor developed by Bial, a Portuguese pharmaceutical company, for conditions including anxiety, Parkinson's disease, chronic pain, and obesity. The Phase I trial was conducted by Biotrial, a French CRO, in Rennes, France. The drug had been tested in 90 volunteers across earlier dose groups without serious issues. In January 2016, the multiple ascending dose phase began with a 50 mg/day group — a dose that was 80 times higher than needed for complete FAAH inhibition.

On 10 January 2016, the first volunteer in the 50 mg group became ill with stroke-like symptoms. The other five subjects received their sixth dose on 11 January before the trial was suspended. All six were hospitalized. Guillaume Molinet, 49, was declared brain dead on 17 January and died. The other four surviving volunteers suffered deep hemorrhagic and necrotic brain lesions, with doctors describing their injuries as 'irreversible handicap.' Two survivors still had memory impairment and cerebellar syndrome nine months later.

The exact toxicity mechanism was never fully determined, but the French regulator's report identified poor target selectivity, excessive dosing, and non-linear drug accumulation at higher doses. Biotrial was criticised for not stopping the trial when the first subject was hospitalised and for not immediately reporting the incident. Bial permanently abandoned the molecule in July 2016. The European Investment Bank had provided €110 million for Bial's FAAH programme. France and the EU revised first-in-human trial guidelines in response.