Molecule is Culprit in French Clinical Drug Trial Disaster
Finally the drug molecule has been nominated as the real culprit for the death of one and severe injuries to five more volunteers in the phase I clinical trial done by France. According to recent report by French National Agency for Drug Safety, the tested compound BIA 10-2474 showed an extremely surprising and unknown effects in brain among a small number of patients.
Phase I trial is the stage one human trial aimed to evaluate drug safety, determine a safe dosage range and identify side effects. According to an article published in Nature the trial was conducted on July 9, 2015 over 128 healthy volunteers in total. Out of these, 90 patients were on drugs and rest were on placebo. At the end of the trial six volunteers from the 90 drug treated group were tested for higher single doses of the same drug, without observing any toxicity. The first participant experienced adverse symptoms on January 11, 2016 later on he died due to brain toxicity on January 17, 2016. Rest of the five patients were also hospitalised due to severity and now they are recovering.
Portuguese based company Bial, designed a new drug (BIA 10-2474) for treating anxiety and related motor disorders associated with Parkinson’s disease; chronic pain associated with cancer and other similar conditions. A French based contract research organization (CRO), Biotrial had performed Phase I trial for this new compound BIA 10-2474. This compound acts by inhibiting an enzyme fatty acid amide hydrolase (FAAH).
Anxiety is a normal emotion but when prolongs, it can cause such severe distress that interferes with one’s ability to lead a normal life. It has been reported that, Anandamide and 2-arachidonoyl glycerol are the two natural endocannabinoids (eCBs) that may contribute to the control of emotions. Fatty acid amide hydrolase (FAAH) is an enzyme responsible for the degradation of these eCBs. So, targeting this enzyme could be considered as a promising candidate for anti-anxiety drugs.
Dominique Martin, director general of the agency, said that the tested drug molecule is solely responsible for the negative effects because no toxicity had been reported from previous trials. In short, the results were totally unexpected. It has been observed and concluded that no manufacturing as well as genetic weakness among volunteers could be responsible for the loss. According to French Health Minister Marisol Touraine, the Biotrial should have stopped the study after the first volunteer got severe, but it continued at the same pace among five more volunteers.
Some evidences came into light that, Biotrial may have ignored preclinical warnings for neurological toxicity. Also, Le Figaro reported that the tested drug have showed similar lethal effects among preclinical animals (rat, dogs and monkeys) as observed in humans. Due to this agency’s experts questioned that why so many animals tested prior to human trials. In general, the agency wants to get experienced.
As per Martin, the regulators has now shared all the documents and findings with other health institutions like FDA and European Medicines Agency. Some top Pharma companies like Pfizer and Sanofi have tested the same molecule in there laboratories but no similar side effects had been reported. Now, investigators are exploring all the study protocols and screening procedure to find the exact reason behind the lethal drug effect. Is it due to drug’s mechanism of action, contaminated doses or any other misconduct?
Recently, Johnson & Johnson voluntarily halted their ongoing studies having similar molecular target (FAAH enzyme blocker) as Bial for anti-anxiety drug. They are planning to get detailed information about the drug and related side effects before further continuing their studies on FAAH blocker.
The reason behind this toxicity is still a mystery, some researcher believe that the concerned drug might be acting “off site” which means it is inhibiting a protein other than FAAH. However, this incident also raises suspicions about FAAH.