One person has been left brain-dead and three others face possibly irreversible brain damage after they took an experimental drug administered to 90 people in France, Health Minister Marisol Touraine and a neurologist said Friday.
Six volunteers were taken to hospital last week after taking part in the Phase I trial of a new medication meant to treat mood disorders such as anxiety, developed by Portuguese pharmaceutical company Bial.
Touraine said the men, aged between 28 and 49, were part of a group of around 90 people who had taken the drug, while about 30 others had received a placebo.
The volunteers were given varying doses and but the six men were in the group who were taking the drug "regularly".
Pierre-Gilles Edan, head of the neurology department at the hospital in Rennes where the volunteers were taken, said that aside from the man who was clinically dead, three others were suffering a "handicap that could be irreversible" and another also had neurological problems.
The sixth volunteer had no symptoms but was being monitored.
"This is unprecedented" in France, said the health minister, vowing to "shed light" on who was responsible.
"The shock is even greater given the fact that the people taking part in clinical trials are healthy."
She said the drug acted on natural receptors found in the body known as endocannibinoids which regulate mood and appetite, but did not contain the compound found in the cannabis plant.
'Tragic but very rare'
The study was a Phase I clinical trial, in which a drug is tested on humans for the first time, after likely tests on animals and in the laboratory to ensure its safety.
Touraine said the drug molecule had previously been tested on chimpanzees.
France's national drug safety body (ANSM) confirmed it was the worst-ever incident to have taken place in a drug trial in the country.
"This type of incident is tragic but very rare in the world of clinical trials," said Professor Jayne Lawrence, chief scientist with Britain's Royal Pharmaceutical Society.
"All medicines have side-effects, but these are generally mild, and severe reactions are incredibly rare."
She said there were very strict regulatory standards in the European Union for such trials and "those in charge of the trial would have had to have shown they had done everything they could to protect patient safety before the trial was allowed to go ahead."
Clinical trials typically have three phases to assess a new drug after preliminary tests on animals and human cells in petri dishes. Human participation in such trials and scrutiny by outside watchdogs are essential for obtaining market authorisation.
After Phase I, Phase II and Phase III are progressively larger trials, typically involving hundreds or thousands of volunteers, to assess the drug's effectiveness.
The trial, which began in July 2015, was being conducted by the privately-owned Biotrial company on behalf of the Portuguese drugmaker.
Biotrial has its French headquarters in Rennes.In a tweet on Friday Biotrial said: "Our thoughts go out to the volunteers and their families" adding that they thanked the medical teams involved for their support.
The research company conducts its Phase I trials at a 150-bed facility in Rennes and also in Newark, New Jersey, from where it carries out "a large variety of early clinical studies," according to its website.
'Followed best practice'
In a statement, the Portuguese firm insisted it had followed "international best practice" in developing the drug and said it would cooperate with the investigation to "determine in a rigorous and exhaustive manner" what had happened.
Based in northern Portugal, Bial says on its website it is Portugal's largest pharmaceutical company with a presence in 58 countries. Founded in 1924, it produces treatments for a range of ailments including problems with the nervous system and cardiovascular health, as well as antibiotics and anti-allergens.
The group which fell ill started taking the drug on January 7 and the first patient began showing negative symptoms on January 10, said Touraine.
Bial halted the trial a day later, she added.
The Paris prosecutor's office said an investigation had been opened.
Every year thousands of volunteers, often students looking to make extra money, take part in such clinical trials which are seen as safe.
Mishaps are relatively rare, but in 2006, six men were hospitalised in London after taking part in a clinical trial into a drug developed to fight auto-immune disease and leukaemia.
One of them lost his fingers and toes and all six reported feeling as if their heads were on fire and their eyes were popping out of their skulls.
In gene therapy, setbacks have included the death of 18-year-old US volunteer Jesse Gelsinger, in 1999, and the development of cancer in two French children treated for "bubble baby" syndrome, a chronic lack of immune defences.