Glaxo Diabetes Drug Is Dealt Fresh Blows

By JEANNE WHALEN

Two new studies dealt fresh blows to diabetes drug Avandia and boosted rival treatment Actos, as Avandia's maker, GlaxoSmithKline PLC, continues to fight safety concerns about one of its major drugs.
The articles, published online by the Journal of the American Medical Association, follow months of debate about the cardiovascular risks of Avandia, which was Glaxo's second-biggest drug last year with global sales of £1.65 billion ($3.35 billion).
The Food and Drug Administration is considering whether Avandia's use should be restricted. In July, an FDA advisory committee found that Avandia was tied to a risk of heart attacks, but stopped short of recommending that the drug be pulled from the market.
Some doctors have been switching their patients to Takeda Pharmaceutical Co.'s drug Actos from Avandia because they have generally perceived Actos as being safer for the heart. The new papers in JAMA could accelerate that trend. One concluded that Actos appears to reduce patients' risk of heart attack, stroke and death. The other paper confirmed some earlier studies suggesting that Avandia raises patients' risk of heart attack. The studies didn't compare the drugs against each other.
Actos is the only other marketed drug that works in the same way as Avandia. Before concerns about Avandia surfaced in May, the two drugs were selling neck and neck in the U.S. By mid-July, Avandia had dropped to 33% of the U.S. market while Actos had soared to 67% of the market. Yesterday, a Glaxo spokeswoman said that Avandia prescriptions have started to rebound over the past two weeks.
Glaxo, in a statement, said the papers "do not confirm a difference in the safety profile" of Avandia and Actos. The studies "do not yield data robust enough to guide doctors in selecting appropriate diabetes treatments for patients," Glaxo said. Glaxo, of the United Kingdom, said the totality of evidence available on Avandia shows that it is as safe for the heart as Actos and other oral diabetes drugs.
Bob Spanheimer, senior medical director for diabetes at Takeda, said the Japanese company would promote the new studies in JAMA about Actos to doctors and patients. Together with other data, the JAMA results "really should give physicians the confidence to prescribe Actos," he said.
In one of the JAMA papers, cardiologists from the Cleveland Clinic analyzed 19 previous clinical trials of Actos and found patients taking Actos had 18% less of a chance of dying from any cause or having a nonfatal heart attack or stroke than those in the control group. Heart attack, stroke or death occurred in 375, or 4.4%, of 8,554 patients taking Actos and in 450, or 5.7%, of 7,836 patients taking other drugs or placebo. The study was funded by Takeda; three of the four authors reported receiving research support or consulting fees from Takeda and other drug companies.
In a separate paper, physicians from Wake Forest University School of Medicine analyzed four clinical trials of Avandia lasting at least one year each. They found that patients taking Avandia had a 42% greater chance of having a heart attack than those in the control group. Heart attack occurred in 94, or 1.46%, of 6,421 patients taking Avandia and in 83, or 1.05%, of 7,870 patients taking other medications or placebo. Similar findings were published in May, by Cleveland Clinic cardiologist Steven Nissen.
Both studies in JAMA were meta-analyses, which means researchers pooled previous clinical studies for analysis. The authors acknowledged that the meta-analysis technique is flawed because it attempts to draw conclusions from studies that were designed and conducted differently.