The FDA On July 21 ordered drug maker GlaxoSmithKline to stop enrolling new patients in a controversial clinical trial of its widely marketed diabetes drug, Avandia (rosiglitazone).
The clinical trial, called TIDE, was mandated by the FDA to assess safety risks of the drug, which is prescribed to treat type-2 diabetes.
But it has been highly controversial because Avandia has been linked in a variety of studies to an increased risk of heart attack and other adverse cardiovascular effects.
Critics, including one of the Food and Drug Administration’s own safety researchers, have said publicly that the trial should be stopped immediately, asserting that it is unethical to expose patients to risks that have been shown statistically to be quite real.
GlaxoSmithKline recently announced that India has already suspended all participation in the TIDE trial in the country.
In India, at least 20 cities including Mumbai, Bangalore, Chennai and Hyderabad had enrolled over 150-200 subjects earlier this year for conducting these clinical trials, which are part of the global post-marketing studies to asses its safety risks.
This development is significant in the wake of the fact that a total of around 2,000 diabetics were to be enrolled from India.
A debate has been raging on the blockbuster drug, Avandia since studies reported serious side-effects like heart attacks and strokes associated with its use, in 2007. It is widely-prescribed by doctors here in India, with 9-10 companies marketing it.
The country’s drug controller general recently halted the trials, for which subjects were being enrolled since February, across various hospitals and clinics all over.
Dr Anoop Misra, director and head diabetes, Fortis Hospitals in New Delhi said: “This step taken by FDA of stopping this unethical trial is welcome, though belated. I hope further step of banning this drug is taken soon. I am also happy to note that DCGI (India) stopped this trial in India before FDA decision, and such efficient steps and regulations are required in India.”
The FDA on its part said its action does not mean the drug will be removed from the market. But the agency is demanding that GlaxoSmithKline update physicians and ethics oversight boards involved in the trial regarding all new safety information about the drug.
It said the information “can be used’’ to update consent forms for new patients and current participants. Critics, including members of Congress, have said the current consent forms in use in the trial are inadequate given the extent of the scientific warning signs.
The potential dangers of Avandia have already discouraged enrollment in the trial.
The trial’s design called for global enrollment of 16,000 patients, with about a third in the United States. But the trial’s lead investigator, Hertzel Gerstein, of McMaster University in Ontario, Canada, said last week only about 1,120 patients had been recruited worldwide, because of the widespread safety concerns.
By a vote of 20 to 12, an FDA advisory panel last week recommended that the drug be permitted to remain on the market. But half of the members who voted to keep it on the market also supported strong restrictions on prescribing, including education programs about the risks for doctors and patients, which specialists predict will dramatically cut into GSK sales figures.
GlaxoSmithKline said in a statement that new enrollment in the trial would be stopped “pending FDA review of recommendations from its Advisory Committee meeting July 13-14. Patients already enrolled may continue in the trial.”
“This pause in enrollment will give clinical trial investigators and patients time to learn about the data presented to the FDA Advisory Committee and the Committee’s recommendations,” said Dr Ellen Strahlman, GSK’s Chief Medical Officer. “We are committed to working with the FDA in the best interest of diabetic patients.”
Avandia, which was approved for the market in 1999, was prescribed 2 million times by US doctors in 2009. It was once the largest-selling drug in its class, with more than $3 billion in global sales. It sold around $1 billion in 2009, with half of that revenue in the US.