Bial trial killed one and brain-damaged four at 40x the therapeutic dose

BIA 10-2474 was an experimental FAAH inhibitor developed by Portuguese pharmaceutical company Bial-Portela for pain and anxiety. On 9 July 2015, a Phase I first-in-human trial began at Biotrial's facility in Rennes, France, with 84 healthy volunteers receiving the drug. The trial was sponsored by Bial, conducted by CRO Biotrial, and approved by the French regulator ANSM.

The drug was an irreversible FAAH inhibitor with poor target specificity. Animal data showed a 45-hour half-life in rats and 104 hours in dogs; several monkeys and two dogs died during testing — facts never disclosed in the trial protocol. Doses escalated from 0.25 mg to 100 mg single doses, then to 50 mg/day multiple doses, despite complete FAAH inhibition achievable at 1.25 mg. The jump from 20 mg to 50 mg was made without pharmacokinetic data from the higher dose. At 40–100 mg, elimination pathways saturated and the drug accumulated in the brain.

On 10 January 2016, the first volunteer in the 50 mg multiple-dose group collapsed with severe neurological symptoms. Biotrial gave the sixth dose the next morning before halting. One volunteer, Guillaume Molinet, died on 17 January. Four others suffered permanent brain damage — haemorrhagic and necrotic lesions in the hippocampus and brainstem. The French regulator ANSM and the EMA overhauled first-in-human trial guidelines as a result.