After a clinical trial in France left one person dead and five others hospitalized last week, there is growing frustration among scientists that little is known about the medicine given to the patients. And under the unusual circumstances, there are calls for the drug maker and French authorities to release some details.
Bial, the Portuguese drug maker whose drug was being tested, has said little publicly about the episode. In its most recent statement, which was released over the weekend, the company would only say that it is “working closely” with French authorities to understand what went wrong. Meanwhile, the French Health Ministry said it is reviewing the trial and expects to issue a report by the end of the month.
At the heart of the mystery is an inhibitor of fatty acid amide hydrolase, or FAAH, an enzyme produced in the brain that breaks down neurotransmitters known as endocannabinoids. The drug reportedly was being developed as a treatment for chronic pain for people with cancer and other ailments. A Phase 1, or early stage trial, began on Jan. 7 in healthy volunteers to gauge drug safety and dosing. About 90 people had been given the tablet at varying doses.
It is not unusual for drug makers to closely guard details of their medicines, notably the structure of a compound, for competitive reasons. A company simply does not want a rival to know the specifics of how a potentially lucrative medicine may work. But in this instance, the lack of information may be an impediment to understanding how similar molecules can function and prevent further harm.
“All we have is an assumption about a specific molecule used in the trial, but we haven’t heard from the company,” said Sean Ekins, an expert in computational toxicology and industry consultant, who has written about transparency issues surrounding the lack of disclosure of chemical structures. “It’s kind of like a cat-and-mouse game. There a little bit of information and we have to try to piece the rest together.
“We would not have this problem if people were transparent about molecule structures. I don’t know if such a tragedy can be prevented by disclosure, but if structure details are out there, it raises the possibility that someone could see an issue. For instance, other companies could test it alongside their own compounds for a problem. There are people who peruse such details for good reason.”
Some scientists have attempted to identify the drug, which is apparently not listed in any of the usual databases where clinical trials are registered. However, Christopher Southan, a pharmacologist and researcher at the University of Edinburgh, and Stephan Alexander, a molecular pharmacologist at the University of Nottingham Medical School, identified the Bial compound as BIA 10-2474.
A Bial spokeswoman confirmed this is the drug, but declined to say whether further information would be released. She only added that, as an FAAH inhibitor, the drug can increase levels of anandamide, a neurotransmitter, which can produce analgesic and anti-inflammatory effects, mood changes, sedation, and vasodilation, among others reactions.
In a blog post over the weekend, Southan argued that there is nothing to stop Bial from submitting the data to databases “in the interests of transparency … Realistically, none of this would help the unfortunate patients in this case, but it could add to our corpus of pharmacological and toxicological knowledge for the future.”
In fact, the company has an ethical responsibility to do so, said Arthur Caplan, who heads the NYU School of Medicine’s division of medical ethics. “There is a duty to release some information so that anyone else using even an analogous agent can be alerted to an issue. That’s where the obligation lies. Protecting human subjects has to come ahead of defending proprietary concerns. That goose is cooked.”
As a result, Thomas Wicks, chief strategy officer at TrialScope, a consulting firm that specializes in disclosure issues, said the episode will “reenergize” calls for greater transparency “as additional details are revealed.”