Questions Remain as to What Caused the Bial Trial Tragedy in France

January 19, 2016 (Updated January 20, 2016, 6 p.m. ET)
By Alex Keown, BioSpace.com Breaking News Staff

CHICAGO -- Days after a Phase I clinical trial studying an experimental fatty acid amide hydrolase inhibitor being developed by Portugal-based Bial-Portela left one patient dead and five others hospitalized in France, there are still numerous unanswered questions, but perhaps most importantly—what went wrong?

FAAH inhibitors are designed to inhibit enzymes which break down endocannabinoids, including anandamide, in the brain and are being investigated for use in the treatment of chronic pain. These molecules activate cannabinoid receptors—the same ones that bind THC, the key component of cannabis, report in Science magazine said. Bial’s BIA 10-2474, the drug tested in the French facility, is designed to inhibit FAAH, and thus slow the breakdown of endogenous cannabinoids, which might help fight pain, the magazine said.

The drug was administered to 108 patients, but only those six were negatively affected, which leads to the unanswered question of “why.” Stephen Alexander, a molecular pharmacologist at the University of Nottingham in the United Kingdom, told Science magazine that it’s possible BIA 10-2474 had “unexpected effects because it binds to another target besides FAAH.” It also could have been a dosing accident, another pharmacologist told the magazine.

There will certainly be further investigations into the trial, which was being conducted by Biotrial, a clinical research organization in Rennes, France.

FAAH inhibitors are being studied by other pharmaceutical companies. Janssen, a division of Johnson & Johnson , is developing a FAAH inhibitor for social anxiety disorder, while Merck and Pfizer are developing FAAH inhibitors for treatment of osteoarthritis pain, insomnia, Tourette syndrome, and cannabis withdrawal, Forbes reported.

Bial has provided few details of the trial, Forbes said, but the company does feature a commitment to transparency of clinical trial information and data sharing on its website. TrialScope, a company focused on clinical transparency management, has called for greater transparency in Phase I trials, citing the TeGenero incident as a reason. Thomas Wicks, TrialScope’s chief strategy officer, told BioSpace that a company had conducted a similar trial about 10 years before the TeGenero incident and abandoned it. Wicks said if that information was public, TeGenero may not have attempted to replicate the trial.

Initially reports said the Bial drug was cannabis based, but it turned out to be a drug aimed at targeting the body’s cannabinoid system. Seth Yakatan, chief executive officer of California-based Kalytera Therapeutics, a company developing cannabinoid-based drugs for the treatment of obesity and osteoporosis, said he spent much of the weekend dispelling rumors about the Bial drug. Because of the inaccuracies being reported, Yakatan said it was important to quell any relationship between the Bial trial and cannabis-based therapeutics.

“This was a bad clinical trial that had nothing to do with cannabis. It’s a story that has gotten out of hand and is not correct,” Yakatan told BioSpace.

There are two medications that contain cannabinoid chemicals in pill form that have been approved by the U.S. Food and Drug Administration. Researchers are investigating the use of cannabinoids for the treatment of several diseases and conditions including HIV/AIDS, multiple sclerosis, Alzhiemer’s disease and pain.