FDA orders GSK to add warning to Avandia

At the request of the US Food and Drug Administration, UK drug major GlaxoSmithKline has added new information to the existing boxed warning on the US packaging of its type 2 diabetes medicine Avandia (rosiglitazone) about potential increased risk for heart attacks.

The agency's ruling is less severe than many analysts had expected, as the FDA also noted that, to date, no other oral anti-diabetes drug has been conclusively shown to reduce cardiovascular risk. Consequently, the regulator has requested that labeling of all approved agents in this class contain language describing the lack of data showing this benefit. This means that the warning could also affect sales of Avandia's rival thiazolidinedione, Actos (pioglitazone), co-developed by Japan's Takeda and US drug major Eli Lilly. Sales of the GSK drug fell after data reported in the May 21 issue of the New England Journal of Medicine linked it to significant risk of heart attack (Marketletter May 28). In the first nine months of 2007, Avandia revenues dropped 14% worldwide to L988.0 million ($2.03 billion), and were down 21% to L650.0 million in the USA.

The new warning now includes a statement that a meta-analysis of 42 clinical studies (mean duration six months; 14,237 total patients), most of which compared Avandia to placebo, showed the drug to be associated with an increased risk of myocardial ischemic events such as angina or myocardial infarction. Three further studies (mean duration 41 months; 14,067 patients), comparing Avandia to some other approved oral antidiabetic agents or placebo, have not confirmed or excluded this risk. In their entirety, the available data on the risk of myocardial ischemia are inconclusive, the FDA noted. Analysts at Lehman Brothers stated that the last sentence of the warning is "more benign than might have been expected."