The Food and Drug Administration will ask a panel of outside medical experts Monday whether it thinks GlaxoSmithKline PLC's diabetes drug Avandia should remain on the U.S. market.
The agency has called a joint meeting of its endocrinologic and metabolic drugs and drug-safety and risk-management advisory committees to discuss whether Avandia raises the risk for heart attacks. Two medical reviewers in the FDA's drug-safety evaluation division said current information involving Avandia "points to an increased risk of cardiovascular adverse events."
GlaxoSmithKline, however, said the totality of the data shows "there is no consistent or systematic evidence that rosiglitazone (Avandia) increases the risk of myocardial infarction or cardiovascular death in comparison to other anti-diabetic agents."
The panel will also be asked if Avandia raises risks for other cardiovascular problems based on clinical studies to be presented at the meeting, and whether "there is evidence that this risk is greater than other available therapies" for type 2 diabetes. The panel will also be asked if Avandia should be limited to certain patients or if a so-called "black box" warning should be added. The FDA typically follows its panels' advice but is not required to.
Safety questions about Avandia surfaced in May when Cleveland Clinic cardiologist Steven Nissen published an analysis of 42 relatively short-term studies involving Avandia that showed an increased risk of heart attacks by 43%. Dr. Nissen is scheduled to serve on the FDA panel as a temporary, nonvoting member. Dr. Nissen has said he doesn't believe Avandia should be taken off the market.
GlaxoSmithKline has strongly defended the safety record of its second-best-selling group of Avandia drugs and criticized Dr. Nissen's analysis because the studies were never designed to assess heart risks. The company sells two other combination drugs under the brand names Avandamet and Avandaryl that include the same active ingredient that's in Avandia. Sales of the drugs totaled $3 billion last year, but the company reported that sales of the drugs fell by 22% in the quarter ended June 30.
Three long-term studies involving Avandia and reviews of patients in insurance databases do not show the same heart attack risk as the short-term studies. Indeed, the FDA said one study known as ADOPT didn't present a "signal" of excess heart attack and cardiovascular deaths.
An introductory memo to the panel from the FDA said, "These various datasets present an array of somewhat inconsistent findings that complicate the interpretation of available data regarding the effect of (Avandia) on cardiac ischemic events." However, another memo dated July 6 from two FDA medical reviewers in the agency's drug risk evaluation division said, "Current available information points to an increased risk of cardiovascular adverse events including heart failure, myocardial ischemica and cardiovascular death in diabetic patients treated with rosiglitazone (Avandia)."
An earlier memo dated Feb. 6 from the same two medical reviewers recommended a "black-box" warning on heart attack risk based on an analysis of 42 short-term studies submitted to the FDA by GSK last year. That analysis showed an overall increased heart attack risk of 31%. Although GSK and Dr. Nissen's analyses both had 42 studies, they were not all the same studies.
An FDA review of the 42 studies first analyzed by GSK showed an overall increased risk among patients taking Avandia of about 40%, but the agency cautioned the results could be swayed by individual studies. Some of the studies showed a higher heart attack rate among small subsets of patients on insulin or who were on other medications to treat cardiovascular disease. The studies included patients on Avandia compared to a placebo, or a fake treatment, and compared to other diabetes drugs or in combination with other drugs.
Avandia and a similar drug, Actos by Takeda Pharmaceutical Co., have long been shown to increase the risk of heart failure, a condition that develops over time and is characterized by the heart's inability to properly pump blood and is different from a heart attack. The FDA has proposed to strengthen existing heart failure warnings on the drugs by adding a "black box" to the drugs' labels. Although Actos is similar to Avandia, the drug hasn't been linked to the same heart attack risk, the FDA said. Monday's meeting will focus on heart attack risks and not the previously known heart failure risks seen with the drugs.
The agency noted that both drugs are effective at reducing the high blood sugar levels that result from type 2 diabetes. Over time, uncontrolled diabetes can lead to other problems such as blindness, kidney disease and cardiovascular disease. About 18 million to 20 million Americans have type 2 diabetes, a disease characterized by high blood-glucose levels that result from the body's inability to use insulin. The disease is typically treated with a variety of drugs and, as it progresses, insulin shots are required.
Glaxo American depositary shares were down $1.19, or 2.3%, at $51.44 in midafternoon trading on the New York Stock Exchange.
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