Biotech Values

[DewDiligence]

FDA Panel Gives Tepid Thumbs-Up for Avandia

[Thus ends perhaps the most unusual FDA advisory panel ever. The vote in favor of keeping Avandia on the market (with or without increased restrictions) was 21-12, while the vote in favor of allowing GSK’s head-to-head study of Avandia vs Actos to continue recruiting and treating patients was 19-11.]

http://online.wsj.com/article/SB10001424052748704220704575367240487934902.html

›JULY 15, 2010
By ALICIA MUNDY And JENNIFER CORBETT DOOREN

A Food and Drug Administration advisory panel voted Wednesday to recommend allowing sales of the diabetes drug Avandia to continue, but said the drug poses a "significant safety" concern because it raises the risk of heart attacks.

It is now up to the FDA to make the final call on whether Avandia, made by GlaxoSmithKline PLC, will remain on the U.S. market. The two-day meeting and the unprecedented job presented to the advisory panel indicate that agency leaders might begin demanding more safety data before new drugs are approved, analysts and researchers say.

FDA officials acknowledged that it was unusual for the agency to ask its advisory committee to directly compare the safety of one drug, in this case Avandia, with a rival medicine, Actos.

Twelve of the panel's 33 members voted to remove the drug, and most of those who supported keeping Avandia on the market said they wanted more restrictions on its use. Many said their vote to retain Avandia was based on the lack of hard evidence about potential harm. They said Avandia should be used only if other diabetes' drugs don't work.

So for now, doctors and their patients still don't have a clear cut signal on what to do because advisory panels' decisions are nonbinding.

Janet Woodcock, the head of the FDA's drug division, said the agency will make a final decision soon and will take the committee's vote into consideration. [Did anyone expect her to say the FDA would *ignore* the panel?]

Wednesday's decision was a relief for Glaxo which has spent the past several weeks settling thousands of lawsuits filed by plaintiffs who say Avandia caused their heart problems.

In a statement, Glaxo defended Avandia's safety. Glaxo Chief Medical Officer Ellen Strahlman said the drug would remain available pending the FDA's decision. "Patients taking Avandia should speak with their physician about their treatment and any questions they may have regarding the safety of the medicine," she added.

Avandia sales have been declining since 2007 when a study in the New England Journal of Medicine linked the medicine to a 43% increase in heart attack risks.

The advisory committee voted overwhelmingly Wednesday that Avandia posed a higher heart attack risk than Actos, which is made by Takeda Pharmaceutical Co.

David Nathan, director of the diabetes center at Massachusetts General Hospital in Boston, said, "Few doctors I know prescribe Avandia on new patients, and many have switched to Actos." He called the data on Avandia "worrisome," but added, "The panel wasn't willing to pull the trigger. I think the FDA will put heavy restrictions on Avandia."

Both Avandia and Actos were approved in 1999 to lower blood-glucose levels for patients with Type 2 diabetes, which affects about 23 million Americans.

Heart failure from excess fluid retention has been a long-recognized problem with Avandia and Actos, and both products already carry the FDA's toughest boxed warning discussing that risk. The issue with Avandia is whether it raises the risk of heart attacks and cardiovascular problems more than other diabetes treatments.

Several panel members expressed conflicted feelings. Panel member David Oakes, a biostatistics professor at the University of Rochester, said his vote to keep Avandia on the market wasn't a "vote of confidence," but reflected concerns about the quality of the data in several Avandia studies linking it to heart attack risk.

The panel voted 19-11 in favor of allowing a Glaxo-funded study known as TIDE to continue in order to compare the cardiovascular risks of Avandia and Actos, if the FDA allows Avandia to stay on the market. TIDE's lead researcher, Hertzel Gerstein of McMaster University, told the panel that study investigators have had trouble recruiting patients, meaning results are unlikely before 2015.

Former FDA Commissioner David Kessler said the Avandia controversy "will chart the future direction of the agency on drug safety," and result in more time and money spent by companies getting drugs approved, and "more safety for the consumer."

Dr. Kessler noted the recall of the painkiller Vioxx in 2004, which was, like Avandia, linked to serious heart problems after it was on the market. "Vioxx and Avandia together have shown the agency and industry that they need to address serious, but common adverse events" before approval.

Tim Anderson, a Sanford C. Bernstein analyst, said investors had already factored in such heightened scrutiny into their assessments of pharmaceutical company stocks, and in the case of Avandia, have been counting on declining sales because of the publicity about safety concerns. [No kidding.]

Since the drug has come under scrutiny, sales of Glaxo's once top-selling drug have slumped. In the first quarter of 2010, world-wide sales of Avandia were about $245 million, down 10% from a year earlier.‹