FDA Scientists Debate Results Of Glaxo Avandia Study

13th Jul 2010 20:14

By Jennifer Corbett Dooren Of DOW JONES NEWSWIRES WASHINGTON (Dow Jones)--FDA scientists debated how to interpret the outcome of a large clinical trial that GlaxoSmithKline PLC (GSK) says backs the safety of its diabetes drug Avandia. Avandia is currently being reviewed by a federal panel that is scheduled to vote Wednesday on whether it thinks Avandia should remain on the U.S. market. FDA Commissioner Margaret Hamburg opened the meeting Tuesday, telling advisers to "follow the science where ever it may lead and the rest will fall into place." Avandia's safety has been in question since a 2007 article in the New England Journal of Medicine by Cleveland Clinic cardiologist Steven Nissen showed it raised the risk of heart attacks by more than 40%. Last year Glaxo released the results of a company-funded study, known as Record, that didn't show an increased heart-attack risk. The study, which involved about 4,500 patients, compared patients on Avandia with those receiving other diabetes drugs, metformin or sulfonylurea for an average of 4.5 years. It showed a similar rate of hospitalizations and deaths among patients receiving Avandia compared to patients on the other diabetes medications. The interpretation of the Record study--funded by GlaxoSmithKline--is an important point because the study is among the key new pieces of information looking at Avandia's safety that has come out since the last FDA panel meeting on the subject since 2007. A similar FDA panel said Avandia appeared to raise the risk for heart trouble but overwhelmingly voted to keep Avandia on the market. Heart failure has been a long-recognized problem with Avandia and Actos, a similar drug made by Takeda Pharmaceutical Co. (TKPYY, 4502.TO). 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 attack and other cardiovascular problems more than other diabetes treatments. Glaxo argued that although the suggestion of increased heart attack risks has mainly been seen in short-term studies, that long-term data, including Record, doesn't suggest an increased heart-attack risk. Murray Stewart, vice president of clinical development at GlaxoSmithKline, said "overall, when used appropriately [Avandia] has a positive risk-benefit profile and should remain a treatment option for patients with type 2 diabetes." However, Thomas Marciniak of the FDA's division of cardiovascular products was critical of Glaxo's Record study, saying it was "inadequately designed and you can't depend on it for safety." Record was designed as a comparative study of diabetes treatments to satisfy a request from the European Medicines Agency and wasn't signed off on by the FDA. Marciniak described problems he found with some case report forms from the study including at least one report of a patient suffering a heart attack that didn't appear to be reported to a committee that was tracking cardiovascular events. Marciniak said a review of 100 case report forms found errors with at least eight forms, including incorrect dates entered for a patient's last visit. "If you can't even decide when you last saw the patients what confidence do you have in complex determinations such as [heart attack] or death," Marciniak said. But Ellis Unger, a deputy director in the FDA's drug division, questioned Dr. Marciniak's interpretations with respect to heart attacks, but said he shared concerns about some of the quality of the data in the study. "There's no clear picture here and if there were you guys would all be back at home," Unger told the panel. Separately Kate Gelperin, an FDA medical officer, described the results of an agency review of 21 studies that compared Avandia and Actos with respect to cardiovascular outcomes. She said outcomes for heart attacks, congestive heart failure and death "favor pioglitazone," or Actos. Later Tuesday, FDA drug-safety scientist David Graham is scheduled to present his recently published study that looked at the outcomes of nearly 230,000 Medicare patients who were treated with Avandia or Actos. The study looked at a combined endpoint of heart attack, stroke, heart failure, or death and found that patients taking Avandia had an 18% increased risk compared to those taking Actos. Graham, also a critic of Avandia, has argued that Avandia should be withdrawn from the market. -By Jennifer Corbett Dooren, Dow Jones Newswires; 202-862-9294; [email protected] (END) Dow Jones Newswires July 13, 2010 15:14 ET (19:14 GMT)