WASHINGTON - U.S. federal health officials are barring new patients from enrolling in a safety study of GlaxoSmithKline's controversial diabetes pill Avandia, a week after a panel of experts ruled that the drug increases heart risks.
The Food and Drug Administration said it issued a "partial clinical hold" on the study to update researchers on the latest concerns about Avandia, which has been under scrutiny since 2007.
Last week a panel of experts voted that the drug appears to increase heart risks, but they ultimately voted to leave the drug on the market because the evidence was not definitive.
The FDA is currently reviewing the panel's opinions and deciding what action to take regarding the trial and the drug itself.
GlaxoSmithKline said in a statement it would halt recruitment for the so-called TIDE trial and update the study's chief investigators on last week's meeting. Patients already in the study will be permitted to continue participating.
The principal investigators of the TIDE trial are from McMaster University in Hamilton -- cardiologist Dr. Salim Yusef and diabetes expert Dr. Hertzel Gerstein.
Gerstein said the TIDE team was informed of the FDA's decision Wednesday morning and immediately got word out to trial sites telling them to stop enrolling new participants.
The study's leadership will need to assess on a weekly basis whether the trial can be completed, he said.
"It is clearly not the optimal environment in which to conduct a trial. But that's just the reality that we're faced with and we have to deal with it in a way that preserves patients' integrity and autonomy," Gerstein said, insisting the leadership team still believes the trial is important to complete.
The London-based GSK agreed to conduct the trial in 2007, after safety questions about Avandia were first publicized.
The TIDE study is designed to give a definitive picture of whether Avandia's heart risks are greater than its chief competitor Actos.
Last week, the FDA's panel of outside advisers voted 20-10 that the trial should continue if Avandia stays on the market.
However, Avandia's critics have argued that the trial is unethical since current evidence already shows Avandia is riskier than Actos, which is made by Japan-based Takeda Pharmaceuticals.
In May, Dr. David Juurlink of Toronto's Sunnybrook Health Sciences Centre and the U.S. patient advocacy group Public Citizen called on the FDA to pull the plug on the trial, saying it would be unethical to ask patients to take a drug -- Avandia -- which had been shown to be more dangerous than the drug against which it was being tested.
On Wednesday, Juurlink said he believes the move may foreshadow bigger developments, maybe even the removal of the drug from the U.S. market.
"To me, that spells the end of the trial, and quite possibly rosiglitazone itself," Juurlink, an internal medicine specialist and drug safety researcher, said via email.
Another prominent critic of the drug applauded the FDA's move.
"It's the ethically correct thing to do," said Dr. Steven Nissen, chairman of cardiovascular medicine at the Cleveland Clinic. "It was the only decision the FDA could have made."
Nissen first drew attention to Avandia's risks in a 2007 New England Journal of Medical article estimating the drug increases heart attack risk by 43 per cent. He noted that the FDA's advisory panel specifically voted last week that Avandia increased risk of heart attacks more than Actos.
The TIDE study is supposed to enrol 16,000 patients, though safety concerns surrounding Avandia have slowed recruitment. GSK reported last week that just 1,100 patients have volunteered for the study.
The FDA first approved Avandia in 1999 and it quickly became the top-selling diabetes pill in the world. However, U.S. sales have plummeted from $2.2 billion in 2006 to $520 million last year as safety concerns swirled around the drug.
The drug works by increasing the body's sensitivity to insulin, a key protein needed for digestion that diabetics don't adequately produce.
The FDA added a black box warning to the drug in 2007. New studies on the drug's safety combined with pressure from safety advocates has prompted the agency to take another look at the drug.
The FDA is expected to make a decision on whether to keep the drug on the market in coming months.
