- The hospitalization of six people participating in a clinical trial for a developmental fatty acid amide hydrolase (FAAH) inhibitor conducted in France has sparked concerns about the overall safety of FAAH inhibitors as a class. One person participating in the trial was initially declared brain-dead, and later died.
- The drug in question was being developed by the Portuguese drugmaker Bial. Janssen (an arm of Johnson & Johnson) had also been developing a FAAH inhibitor but decided to halt its trial on January 17 after news of the Bial disaster broke. Sanofi and Pfizer have also worked on FAAH inhibitors in the past.
- FAAH inhibitors work by slowing the degradation of anandamide, a "feel-good" molecule, as well as several related endocannabinoids. Bial's compound was aimed at treating major anxiety and depression.
FAAH has been considered an attractive target by researchers because of its potential to address various neurologic and psychiatric conditions. Until now, no serious adverse events had ocurred in the phase 1 and phase 2 trials conducted by Sanofi, Pfizer, and Janssen. However, the Bials' trial of BIA 10-2474, conducted by the testing firm Biotrial, has called the safety of the entire class into question.
However, experts think the serious adverse events which occurred in the Biotrial-tested patients may be related more to dosing than a lack of safety for the entire class. It could also be related to a lack of specificity for the FAAH target, making off-target activity possible.
Bial had been testing its compound in an escalating-dose study. Over one hundred patients had been administered with the drug before the six were hospitalized. Those six had received multiple doses, more than others in the trial, according to Fierce Biotech.
This event could possibly dissuade interested companies from pursuing further research efforts. Bial's compound was being tested for the first time in humans as part of phase 1 safety trials. Janssens' drug had advanced beyond Phase 1 and into further study. Janssen indicated it would reevaluate its decision when it had more information .