UPDATE: FDA Staff Raise Concerns About Avandia Safety, Glaxo Study

9th Jul 2010 18:12

(Updates with additional comments and background.) By Jennifer Corbett Dooren Of DOW JONES NEWSWIRES WASHINGTON (Dow Jones)--Food and Drug Administration staff scientists continued to question the safety of GlaxoSmithKline PLC's (GSK) diabetes drug Avandia, according to new agency documents released Friday. The documents were prepared for an FDA advisory panel meeting next week that will discuss Avandia's safety and vote whether it thinks Avandia should remain on the U.S. market. The agency's drug safety and the endocrinologic and metabolic advisory committees will hold a joint two-day meeting and is scheduled to vote on several questions on Wednesday. The safety of Avandia has been in question since a 2007 article in the New England Journal of Medicine by Cleveland Clinic cardiologist Steven Nissen showed the product raised the risk of heart attacks by more than 40%. New data released last week added to the controversy with two studies concluding that Avandia has safety problems and one--an analysis of a government-funded study looking at treatments in people with diabetes and heart disease--suggesting Avandia didn't increase heart attack risks. In 2009 Glaxo released the results of a company-funded study known as Record that didn't show an increased heart-attack risk in a study that involved about 4,500 patients. The study compared Avandia to patients receiving other diabetes drugs, metformin and sulfonylurea, for an average of 5.5 years. The results of that study were among the studies discussed in the 765-page briefing document the FDA posted to its website Friday. A memo from Thomas Marciniak, a medical team leader in FDA's division of cardiovascular and renal products, said the Record study was "inadequately designed and conducted to provide any reassurance about the CV (cardiovasular safety) of rosiglitazone." Rosiglitazone is the generic name for Avandia. Marciniak said the Record results "confirm and extend the recognized concerns regarding heart failure" and possibly suggest an increased risk for heart attacks. Heart failure has been a long recognized problem with Avandia and Actos, a similar drug made by Takeda Pharmaceutical Co. (TKPYY, 4502.TO) and both products carry the FDA's toughest boxed-warning discussing that risk. The issue with Avandia is whether it raises the risk of heart attack and other cardiovasular problems more than other diabetes treatments. However, another memo from Ellis Unger, a deputy director in FDA's drug division, questioned some of Marciniak's interpretations and said the "study does not appear to demonstrate harm" with respect to heart attacks. In a statement, Murray Stewart, vice president for clinical development at GlaxoSmithKline, said, "since 2007 we have seen results from six controlled clinical trials looking at the cardiovascular safety of Avandia and together they show that this medicine does not increase the overall risk of heart attack, stroke or death." Earlier Friday, the European Medicines Agency said its Committee for Medicinal Products for Human Use would discuss Avandia's safety at its next meeting July 19-22. The CMPH will then issue an opinion about whether the marketing authorizations for Avandia and other products that contain the same active ingredient "should be revoked, suspended or changed." FDA's panel is being given several options with regard to how it votes on Avandia, including allowing the product to stay on the market or adding restrictions on the use of the product such as only allowing certain doctors to prescribe the medication. In 2007 a similar FDA panel said Avandia raised "cardiac ischemic" risk, which is a reduction in blood supply to parts of the heart, but voted 22 to 1 in favor of keeping the product on the market. The FDA usually follows the advice of its panels but is not required to. "The meeting is going to be about the best information we have on the safety of Avandia," said Joshua Sharfstein, FDA's principal deputy commissioner. He said the agency would aim to make a "timely" decision after the panel meeting. Janet Woodcock, the head of FDA's drug division, suggested the agency was still struggling with Avandia. "There's not complete unanimity within FDA as to the interpretability of these data," she said. "That's why we are going to panel." Along with the Record study, the panel will discuss other data including an updated analysis by Nissen released last week and a study lead by FDA drug-safety scientist David Graham. That study looked at the outcomes of nearly 230,000 Medicare patients who were treated with Avandia or Actos and found those on Avandia had an 18% increased risk of having a heart attack, stroke, heart failure or death compared to those on Actos. Avandia was once a multibillion-dollar-a-year medicine and one of Glaxo's top-selling drugs. Since the drug has come under attack, sales have slumped. In the first quarter of this year, world-wide sales of Avandia were about $245 million, down 10% from a year earlier. Avandia was approved in 1999 as a treatment for Type 2 diabetes, the most common form of the disease, and is designed to lower blood-glucose levels. Diabetes is a disease that affects about 24 million Americans and is characterized by high blood glucose levels caused by the body's inability to either make or properly use insulin. Type 2 diabetes is the most common form of the disease and is often associated with weight-gain and older age. (Type 1 is an autoimmune disease often diagnosed in children in which the body's immune system destroys pancreatic beta cells that produce insulin). -By Jennifer Corbett Dooren, Dow Jones Newswires; 202-862-9294; [email protected] (END) Dow Jones Newswires July 09, 2010 13:12 ET (17:12 GMT)