Glaxo's Avandia to get tougher heart risk label

11/15/2007- GlaxoSmithKline PLC's Avandia, the world's best-selling diabetes drug last year, will carry US regulators' strongest warning on the risk of heart attacks.

The London-based drug maker agreed to provide the warning, outlined in a black box in Avandia's prescribing information, the Food and Drug Administration said yesterday. The agency is continuing its assessment of Avandia's safety, including whether it poses greater dangers than competing products such as Takeda Pharmaceutical Co.'s Actos.

Avandia was Glaxo's second-biggest drug last year after the asthma treatment Advair, generating revenue of $3.3 billion. US sales dropped by about half after a May 21 report in the New England Journal of Medicine by Cleveland Clinic researchers linked Avandia to a 43 percent increased risk of heart attacks. The FDA's action fell short of restrictions on Avandia that were put in place in Canada and Europe in recent weeks.

"They dodged a small nuclear explosion," said Navid Malik, an analyst at Collins Stewart in London. The FDA hasn't "allowed Actos to claim a benefit, but they haven't killed Avandia."

Health Canada withdrew approval for Avandia as a stand-alone therapy last week and said it should be given mainly with the older drug metformin. European regulators said it should be used only in select groups of patients.

Glaxo's American depositary receipts, each equal to two ordinary shares, fell 61 cents to $49.99 in New York Stock Exchange composite trading.

"We want to make sure that healthcare providers and patients are aware that this signal of a risk has been identified," said John Jenkins, director of the FDA's Office of New Drugs, in a conference call with reporters. "As we wait for more definitive studies to be completed, we want to make sure they take that into account."

Glaxo has agreed to the FDA's request to conduct a new trial of Avandia, and the agency will ask that the medicine be compared directly with Actos and perhaps other drugs, said Janet Woodcock, acting director of the agency's Center for Drug Evaluation and Research, on a conference call with reporters.

The trial will start next November and last four to five years. Results won't be available until 2014, but interim analyses of the data should provide the agency and doctors with some guidance on the drug's safety, she said.

"We are keeping Avandia on the market because we have concluded there isn't enough evidence to indicate that the risk of heart attack" or of reduced blood flow to the heart is higher with Avandia than with other pills to treat diabetes, Woodcock said.