The Food and Drug Administration has ordered tougher warnings for diabetes drug Avandia (rosiglitazone), as well as a similar drug, Actos. The new mandate was announced by FDA Commissioner Andrew von Eschenbach at a congressional hearing yesterday, where the FDA was being scrutinized and questioned about why it didn't act sooner even though outside experts drew attention to cardiac risks years ago. "The FDA dropped the ball," said Rep. Henry Waxman, the California Democrat who heads the oversight committee that held yesterday's hearing.
Still, the new black box warnings will address only the risk of congestive heart failure, not the increased risk of heart attack suggested by a controversial study recently published in the New England Journal of Medicine. The FDA has not required stronger warnings about heart attacks because it is still reviewing dozens of often contradictory studies and analyses on Avandia's effect on diabetic patients. In fact, the FDA has scheduled a July 30 meeting of outside experts who will review the data.
Officials at GlaxoSmithKline rushed to publish preliminary results of a clinical trial before yesterday's hearing, contending that the results show that Avandia carries the same risk of heart attack and cardiovascular disease as other diabetes drugs. But influential doctors said that the data published just before the hearing does nothing to ease their concerns about cardiac risks.
GlaxoSmithKline was asked to explain its apparent attempt to intimidate diabetes expert Dr. John Buse, head of the University of North Carolina Diabetes Care Center, and soon to be president of the American Diabetes Association. Dr. Buse first questioned the safety of Avandia at a medical conference in 1999. Soon after, his department head received a call from a high-ranking official at GlaxoSmithKline's predecessor, SmithKline Beecham, threatening to hold Dr. Buse responsible for its $4 billion decline in stock, characterizing Dr. Buse as a liar, and alleging that he was "for sale." Dr. Buse responded with a strong letter, saying in part, "I may disagree with SB's interpretation of data. I am not for sale. . . . Please call off the dogs. I cannot remain civilized much longer under this kind of threat." Dr. Buse said that he later "signed a clarifying statement drafted by SB" to be used with the "investment community."
The U.S. Senate Committee on Finance has also asked the FDA to answer to allegations that an official within the FDA was verbally reprimanded in March of 2006 for recommending a black box warning regarding congestive heart failure, a potentially fatal condition where fluid build-up in the lungs causes severe shortness of breath. Dr. Rosemary Johann-Liang said she was ordered by FDA officials who work more closely with GlaxoSmithKline to retract her approval of the warning, lost her power to approve such assessments, and no longer supervised reviews of the safety of Avandia and Actos. "This was a very careful review that came to an inescapable conclusion. They decided to act like the review never happened and punish me for approving it," said Dr. Johann-Liang.
Until the dust and controversy settles down and experts can agree on the relative heart risks of Avandia, the American Diabetes Association (www.diabetes.org) strongly recommends that patients on Avandia talk to their doctors about the recent concerns.