By Ben AdamsFrench Health Minister Marisol Touraine
The fault for the death of one patient and the serious injuries to 5 others in a French drug trial is down to the medicine itself, rather than the CRO and pharma company conducting the study.
This is according to a new report by the French National Agency for Drug Safety, released this week, which said the compound being tested--BIA 10-2474--produced an "astonishing and unprecedented" reaction in the brain of a small number of patients, which could not have been foreseen.
In all, 90 patients had taken the drug, but in January, 6 trial participants took a higher-dose form of the treatment (10 times greater than required), with one becoming brain dead and later dying. Five others were seriously ill, but reports suggest that they are now recovering.
The Phase I trial was being undertaken by the French CRO Biotrial on behalf of Portuguese drugmaker Bial for BIA 10-2474, a medicine that blocks the enzyme FAAH to treat anxiety.
Dominique Martin, director general of the agency, said of the report: "It is clearly the molecule that is the cause. The common element between the victims is indeed that molecule."
He added, as reported by French newspaper Le Monde: "There was no warning [of toxicity] from the first volunteers. It is as if a dam had burst somewhere."
The initial report ruled out any manufacturing problems and said there was no shared genetic weakness among the victims, who suffered similar damage to the same part of the brain.
But questions still remain. French Health Minister Marisol Touraine said a month ago that Biotrial "should have halted the tests" after the first person was hospitalized. This didn't happen, however, and 5 more people were given the medicine the next day.
And several weeks ago, new evidence came to light that Biotrial may have ignored preclinical warning signs of neurological damage. This allegation came when Le Figaro reported it had seen information that an early-stage animal study of the drug had left "a number" of dogs dead and other animals suffering with serious side effects similar to those seen in the fatal human study.
The agency's experts have in fact questioned why so much animal testing had preceded the human trials. They said it was "surprising to see that rats, mice, dogs and monkeys were all used"--raising the question as to whether there were concerns over side effects.
But in general, the agency wants to learn from the trial. "What matters now is what action can be taken: there is a before and after," said Martin.
He added that the regulator has now forwarded all the scientific documents relating to the study on to other health agencies, including the FDA and European Medicines Agency--although Bial is reported by Le Monde to have raised concerns about others seeing the IP around the study.
A number of Big Pharma companies, including Pfizer ($PFE) and Sanofi ($SNY), have tested similar molecules before, but their studies failed to find bankable efficacy. No serious neurological side effects were ever noted in these companies' tests.
A full and more detailed report from the agency will be published on March 24.
- read Le Monde's story (translated)