Avandia’s Reckoning Day
Sep23

Avandia’s Reckoning Day

After years of debate over the safety of GlaxoSmithKline’s diabetes drug Avandia, U.S. and European regulatory agencies have finally made a decision about the future of the drug. European authorities have recommended suspending marketing of the drug, while FDA is severely restricting access to the drug, but seems to be leaving the door open to further actions. GSK, meanwhile, issued a press release saying it would stop promoting Avandia worldwide. Today's announcements mark yet another chapter in the Avandia saga, which began in May 2007, when Cleveland Clinic cardiologist Steve Nissen published an analysis of the combined data from 42 previous clinical trials of GSK’s diabetes drug. The results weren’t pretty: Nissen’s article in the New England Journal of Medicine claimed that patients taking Avandia were 43% more likely to have a heart attack than those who were not on the pill. The next three years brought a series of safety alerts, conflicting data analyses, advisory panels, and questions over whether GSK tried to cover up the cardiovascular safety risk associated with the drug. In July, a panel of FDA advisors had mixed views on Avandia: 12 of the 33 panelists voted to remove the drug from the market, while 10 said it could stay on the market with strong restrictions on prescribing the drug. FDA today sided with those 10 panelists and imposed strict limitations on who can take Avandia. The agency will also adjust the drug's label to reflect the safety risk. Under a risk evaluation and mitigation strategy, or REMS, Avandia can only be prescribed to new patients if they have been unable to control their blood sugar with other diabetes drugs. People already taking Avandia can continue taking the drug, but will have to register in the REMS program and sign a document saying they are aware of the cardiovascular concerns associated with the drug. FDA did not provide a clear timeline on how long it would take to implement the REMS. “We believe this action will severely limit the number of people on this drug,” Janet Woodcock said this morning in a conference call with reporters. FDA believes the REMS requirement will cause diabetics to “think twice” before they continue on the drug or start taking it, she said. FDA said about 600,000 people are currently taking Avandia, a number that the agency believes will drop precipitously under these new requirements. Patients will surely be confused by the mixed messages being sent by the agencies: after all, if it’s not safe in Europe, why would it be safe here? FDA defended its action by pointing out that European regulatory authorities lack the ability to...

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Future Cloudy for GSK’s Avandia
Jul15

Future Cloudy for GSK’s Avandia

A panel of FDA advisors decided yesterday that GlaxoSmithKline’s diabetes drug Avandia should either be withdrawn from the market or its use seriously restricted. The panel had been assembled after several years of ongoing questions over the safety of the drug, which has been linked to an increased risk of cardiovascular events. The final vote came down to this: 12 panel members said the drug should be removed from the market, while 10 said it could stay on the market, but with strong restrictions on who could both prescribe and take the drug. The remaining members voted to either keep the label the same or revise it somehow to better reflect the safety concerns. With that mixed bag in hand, its up to FDA to decide what to do. For those of you having trouble keeping track of the ins an outs of the Avandia story, here’s a little primer. GlaxoSmithKline’s Avandia problems—the public ones, at least—began in May 2007, when the safety of the drug was questioned by Cleveland Clinic cardiologist Steve Nissen, previously known for blowing the lid off the cardiovascular issues associated with Merck’s arthritis drug Vioxx. In an article in The New England Journal of Medicine, Nissen said an analysis of the combined data from 42 previous clinical trials of Avandia showed that patients taking the drug were 43% more likely to have a heart attack than those who weren’t. FDA issued a safety alert about the drug, which brought in $3 billion for GSK in 2006. In August 2007, an FDA advisory panel voted 22-1 to keep Avandia on the market. Still, Avandia franchise sales fell 22% to $2.4 billion in 2007. But GSK’s troubles with Avandia go beyond the financial pain of lost sales. As you might expect, the company is at the receiving end of a flood of lawsuits related to the drug. It could get worse. This week, the NY Times said it had reviewed internal documents suggesting GSK knew as early as 1999 that the drug posed a safety risk, but actively worked to conceal those findings from FDA. Yesterday, GSK said it would take a charge of $2.36 billion in the second quarter, in part to help pay to settle lawsuits related to Avandia and its antidepressant Paxil. Avandia works by lowering blood glucose levels by increasing cells' responsiveness to insulin. This isn’t the first time drugs acting on Avandia’s target, the peroxisome proliferator-activated receptor (PPAR), have run into safety trouble. In 2005, Merck and Bristol-Myers Squibb withdrew a New Drug Application for their PPAR agonist Pargluva after FDA asked for a five-year cardiovascular safety study. And Warner-Lambert pulled...

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