US FDA Adds Warning To Diabetes Drug Avandia

Woodcock said various studies looking at the safety of Avandia cannot say clearly whether Avandia itself raises the risk of heart attack.

GlaxoSmithKline Plc's diabetes drug Avandia will carry a stern "black box" warning that says the drug could cause heart attacks, the U.S. Food and Drug Administration said on Wednesday.

The company will also design and start a trial comparing Avandia head-to-head with a rival drug, Takeda Pharmaceutical Co Ltd's Actos, to see whether the risk is unique to Avandia, the FDA said.

"We are keeping Avandia on the market because we have concluded that there is not enough evidence to conclude that the risk for heart attack or cardiac ischemia is higher than for other type-2 diabetes drugs," the FDA's Dr. Janet Woodcock told reporters in a telephone briefing.

Woodcock said various studies looking at the safety of Avandia cannot say clearly whether Avandia itself raises the risk of heart attack. The studies that appear to show a risk all compare Avandia with a placebo, she said.

The top-selling diabetes drug has been under scrutiny since a U.S. analysis last May linked Avandia to a 43 percent higher risk of heart attack in patients.

But the news did not strongly affect Glaxo's share price, which was down less than 1 percent at $50.13 a share on the New York Stock Exchange after the announcement.

Avandia and Actos both already carry strong warnings advising of the risk of a different side effect -- heart failure, a chronic condition that affects the heart's ability to pump blood.

Millions of diabetics around the world take Avandia. It was Glaxo's second-biggest drug in 2006 with sales of $3 billion but its use has dropped heavily.

Avandia, known generically as rosiglitazone, and rival drug Actos, known generically as pioglitazone, were designed to make the body more sensitive to insulin, a hormone the body needs to convert sugar into energy.

REDUCING COMPLICATIONS

They are part of a family of drugs called thiazolidinediones and are among several classes of drugs that treat type-2 diabetes, which affects 194 million people worldwide.

The FDA officials said they are meant to reduce common complications of type-2 diabetes such as blindness or limb loss, but not to reduce the most fatal outcome, which is heart disease.

"Avandia remains a safe and effective medicine for most patients with type-2 diabetes when used appropriately," said Dr. Ronald Krall, Glaxo's chief medical officer, said in a statement.

"Given the severity of this disease and the importance of Avandia in helping patients manage their diabetes, we will continue to work with the FDA to conduct more studies about the safety and benefits of our medicine."

FDA officials said they consulted widely before making the decision. Two different advisory committees voted on whether to keep Avandia on the market, Woodcock said.

Members of the Endocrine and Metabolic Drugs and Drug Safety and Risk Management Advisory Committees voted 22-1 to recommend that Avandia stay on the market.

The FDA's safety committee also considered the issue but the FDA officials did not disclose how that vote broke down. "We took into account a very broad variety of opinions," Woodcock said. "We don't expect everyone to agree at the end of the day."

Meanwhile, Glaxo will prepare a study that will show whether Avandia does raise the risk of heart attacks or clogged heart arteries more than any other diabetes drugs. The study design will be prepared by next July and the study will be completed by 2014, FDA's Dr. John Jenkins said.

But the agency will review data as the study proceeds, in case there is a clear indication that something is going wrong.

"It isn't as if we are going to be clueless until 2014," Woodcock said.