Days after receiving the experimental medication BIA 10-2474 in a first in human trial, one man was brain dead and another five hospitalized. According to recent reports, three are likely to have neurological deficits.
To my knowledge, this is the first time since 2001 that a healthy volunteer has died in a medical experiment. And it is the first major drug disaster in a phase 1 trial since 2006, when six men were hospitalized after developing a life threatening (but not ultimately fatal) immune response to the drug TGN1412.
Details surrounding the BIA 10-2474 trial are sketchy – and are likely to remain so as long as a manslaughter investigation is underway. Here is what we do know. The drug was a small molecule inhibitor of an enzyme involved in endocannabinoid metabolism, fatty acid amide hydrolase (FAAH). Other FAAH inhibitors have been tested in human beings without incident. Nor have any shown clinical activity. We also know that the men who developed life-threatening toxicities were the first to receive multiple doses of BIA 10-2474. And, based on a study protocol released by Le Figaro, multiple doses within this cohort were not staggered.
Healthy volunteer phase 1 studies are creepy. The realm of phase 1 testing is secretive, and most studies are conducted in private contract research organizations rather than academic medical centers. Few studies are ever published. Indeed, drug regulators exempt companies from even registering them in public databases. This makes it difficult to know anything about their volume, record of safety, the demographics of study participants, or the nature of study procedures.
The views, opinions and positions expressed by these authors and blogs are theirs and do not necessarily represent that of the Bioethics Research Library and Kennedy Institute of Ethics or Georgetown University.