A U.S. Food and Drug Administration official called for higher safety standards in approving diabetes drugs in the aftermath of fears about links between a top diabetes drug and heart attack risk.
The safety of GlaxoSmithKline's Avandia and other diabetes drugs was thrust into the spotlight after a New England Journal of Medicine analysis in May linked Avandia to a 43 percent increase in risk of having a heart attack.
Now, the FDA medical reviewer of Glaxo's original application for Avandia is calling for experimental diabetes drugs to be tested against existing drugs, instead of the traditional method against a placebo, that official wrote in the December issue of the journal Diabetes Care, released on Tuesday.
"You can't really evaluate a drug in a vacuum; you have to evaluate it in comparison to something," Dr. Robert Misbin, a medical officer in the FDA unit that reviews diabetes drugs, said in an interview.
Avandia had sales of more than $3 billion last year, but sales have slipped to rival Actos made by Takeda Pharmaceutical Co. amid the controversy.
According to the World Health Organization, about 180 million people worldwide suffer from some form of diabetes, a condition where the pancreas can't produce enough of the blood-sugar regulating hormone insulin, or can not use effectively what it produces.
The FDA has since added its strongest labeled warning to Avandia, while lawmakers have criticized the agency for minimizing safety concerns about the drug.
An FDA panel of experts earlier this year voted to keep Avandia on the market, despite the risks, saying the evidence was too thin to halt sales. FDA took that advice, but earlier this month added a "black box" warning of the studies suggesting risk.
"The FDA should not ignore the perceived shortcomings in the regulatory process that allowed the Avandia affair to get out of hand," Misbin wrote.
Drugmakers in general now test their drugs against a placebo to win regulatory clearance in the United States.
Companies have no incentive to test their drugs against rivals, and so the FDA should require them, given the efficacy of current treatments for diabetes, Misbin said.
Pharmaceutical companies in recent months have complained that the FDA is raising the bar for approving new drugs by in effect comparing experimental treatments with current therapy.
But a top FDA official told Reuters earlier this month that although there is a renewed focus on safety, the agency always has taken comparable drugs' safety record into account when reviewing drugs.
Misbin wrote that although the FDA doesn't have the authority to require that a new drug be superior to existing treatments, the FDA "is not required to have proof that a new drug is unsafe to deny approval."
He added that the FDA should "set a high standard for drugs that offer no advantage over existing therapy."
Misbin's original advice to require Glaxo conduct a post-marketing safety study as a condition for Avandia's approval was not taken by his superiors.
A safety trial should be required — before approval — of all diabetes drugs, Misbin advises.
While the FDA evaluates safety data as part of its clinical trials for approving a drug, Misbin is calling for a separate trial designed specifically to detect major safety problems. And that trial should not exclude patients at risk for serious adverse events, he said.