French drug trial disaster leaves patient dead amid a slew of unanswered questions

The patient left brain-dead in last week's botched drug trial has died, French authorities said, spurring more questions about how a routine Phase I study went awry and sent 6 volunteers to the hospital.

The patient, dosed with an investigational drug from Portugal's Bial, died Sunday, about a week after the company's CRO halted the study in response to serious side effects. The 5 other hospitalized patients remain in stable condition, according to the French government.

In the ensuing fallout, regulators and scientists are struggling to piece together what went wrong in the trial. Bial's drug is meant to treat mood and motor disorders by blocking the enzyme FAAH, the company said. Before the recent rash of hospitalizations, the drug was administered to 108 patients with no severe side effects, according to the company. And FAAH is not a novel biological target: Merck ($MRK), Pfizer ($PFE) and others have run clinical tests on drugs aimed at the enzyme without running into such serious neurological risks.

Bial's trial, run by French CRO Biotrial, was an escalating-dose study, recruiting healthy volunteers to determine the maximum tolerability of the candidate drug. As Science reported over the weekend, the 6 hospitalized volunteers received multiple daily doses of the treatment, more than previous trial participants, and began showing symptoms of brain damage within three days. French health minister Marisol Touraine said in a news conference on Friday that investigators had yet to determine whether the problems were related to the drug's mechanism of action or the result of contaminated doses.

For its part, Bial called the trial a "tragic and unfortunate situation," saying the company's "thoughts and solidarity go out to the family" of the volunteer who died. The drugmaker also noted that it obeyed international guidelines in preparing the trial, completing the requisite preclinical tests and toxicology screens before enrolling patients. French regulators approved Bial's plans for a Phase I trial based on those results, the company said, and Biotrial has claimed that its work was done in compliance with international regulations.

"Together with all the relevant authorities, Bial is strongly committed to ensuring, first of all, the well-being of all participants in this trial and to determine thoroughly and exhaustively the causes which are at the origin of this situation," Bial said in a statement.

The University Hospital of Rennes, which admitted the 6 patients, is now reaching out to all of the trial's volunteers, bringing in each for neurological screens.

- read the government's statement
- check out Bial's release
- here's the hospital's disclosure
- and Science's story

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