February 26, 2016
By Alex Keown, BioSpace.com Breaking News Staff
PARIS – An experimental chronic pain treatment that caused one death and left five others with possible brain damage in a French clinical lab was believed to be related to deaths in dogs in earlier clinical testing, the Telegraph of London reported this morning.
The Telegraph reported the details of the canine deaths were not reported by the laboratory conducting the tests for Portugal-based Bial-Portela were not disclosed due to “industrial secrecy.” The trial was being conducted by Biotrial, a clinical research organization in Rennes, France. Citing a report in the French paper Le Figaro, the Telegraph said a “number of dogs” died and others suffered neurological damage in preclinical trials of the drug. Bial has refused to reveal information about the preclinical data and the canine deaths.
François Peaucelle, the director of the drug evaluation company, told the Telegraph the deaths of the dogs were not significant and did not impact the safety of going forward with human trials. Additionally, the contract between Bial and Biotrial “requires the drug evaluation company to obtain the manufacturer’s agreement before disclosing information about the medication or the trial,” the Telegraph said.
The lab was conducting a Phase I clinical trial studying an experimental fatty acid amide hydrolase inhibitor being developed by Bial. FAAH inhibitors are designed to 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, a 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.
There are still numerous unanswered questions, but most specifically, what went wrong with these six patients. The drug was administered to 108 patients in varying doses, but only those six were negatively affected. The patients who were hospitalized had received the highest dose of the drug during the trial, the minister said. The five patients have since left the hospital and returned home and will be given another health check up at the end of February, she said.
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. However, following the French lab accident, Johnson & Johnson said on Jan. 21 that it was voluntarily suspending its FAAH trials.
Since the death and hospitalization, Biotrial has been criticized by the French Health Ministry, who said officials at the lab were slow to react after the first patient fell ill. However, the ministry said no regulations appear to have been breached during the trial. The ministry said the trial should have been halted after the first patient was hospitalized, but the drug was administered to five more people the next day.
Biotrial has maintained that it had “strictly complied to international standards.”
“The trial has been conducted in full compliance with the international regulations and Biotrial’s procedures were followed at every stage throughout the trial, in particular the emergency procedures for the transfer of volunteers to the hospital,” the company said in a statement on its website.
Since the fatality in the Bial trial, Johnson & Johnson voluntarily halted its own trials of an experimental fatty acid amide hydrolase inhibitor although the company said it did not notice any adverse dosing effects. The company said it would reevaluate the trials when it has more information.
Other pharmaceutical companies are developing FAAH inhibitors, including Merck and Pfizer, which are developing FAAH inhibitors for treatment of osteoarthritis pain, insomnia, Tourette syndrome and cannabis withdrawal.
