Glaxo’s Avandia Should Be Pulled, U.S. Scientist Says
(Update2)
By Justin Blum and Michelle Fay Cortez
July 30 (Bloomberg) — GlaxoSmithKline Plc’s diabetes pill Avandia should be removed from the market because of heart risks, a U.S. drug safety scientist said.
There is “no evidence of major clinical health benefits'’ from Avandia and leaving it on the market may “cost thousands of lives,'’ according to slides for a presentation to be given today by David Graham, a Food and Drug Administration safety scientist. Graham is set to speak today to FDA advisers meeting in Gaithersburg, Maryland to review studies of the drug.
Graham’s presentation may raise the likelihood the panel will urge that the drug be removed from the market, or receive a heightened warning. Glaxo’s shares fell 6 pence to 1,219 pence in London, and the company’s American depositary receipts dropped 8 cents to $49.55 at 9:31 a.m. in New York Stock Exchange composite trading. One depositary receipt equals two ordinary shares.
Graham’s slides, released by the FDA before the panel meeting began, question Avandia’s health benefits compared with other treatments. Graham’s recommendation doesn’t represent the FDA’s position and he has disagreed with his superiors in the past. He gained notoriety after calling for Merck & Co.’s painkiller Vioxx to be pulled from the market long before it was withdrawn in 2004 because of heart risks.
“Patients have been scared enough by a lot of snippets of information here and there,'’ said Chris Viehbacher, president of U.S. pharmaceuticals at Glaxo, in an interview today. “The advisory committee’s going to hear a lot of people, including Dr. David Graham, and I think what you’re going to find is that the weight of scientific evidence continues to support the safety of Avandia.'’
Journal Report
Before today, the stock had fallen 16 percent since a May 21 report in the New England Journal of Medicine tied Avandia to a 43 percent increased risk of heart attacks. In February, drug- safety scientists at the FDA concluded Avandia shouldn’t be used with insulin or by patients with heart disease, according to documents posted on the agency’s Web Site July 26.
The FDA often follows the advice of its advisory panels, though the agency isn’t required to do so.
Graham’s recommendation doesn’t mean the FDA will pull the drug from the market, said Navid Malik, an analyst at Collins Stewart in London, in a telephone interview today.
“He obviously made a good call about Vioxx, but these guys, they’re very vocal, they sometimes go against the grain of what the evidence is saying,'’ Malik said. “I’m not sure the reasons he cited for the withdrawal correlate with the evidence. He cites cardiovascular risks but there are data which are contradictory.'’
Glaxo Documents
Numerous studies involving thousands of patients show there is no additional danger with Avandia, Glaxo said in documents it submitted to the FDA before the meeting. The drug remains an important treatment choice for patients with type 2 diabetes, the most common form, the London-based company said.
The question raised by the May report conducted by Cleveland Clinic researchers “has not been confirmed across more robust and definitive data sources,'’ according to Glaxo, the second-biggest drug company in the world after Pfizer Inc.
“There is no consistent or systematic evidence'’ that Avandia increases the risk of heart attacks or death from cardiovascular disease compared with other drugs, it said.
The FDA meeting, composed of nearly two dozen experts from the agency’s diabetes and drug safety advisory committees, will cover more than 600 pages of data and dozens of studies on Avandia. The agency asked the panel to vote on whether existing information “supports the conclusion'’ that Avandia increases cardiac risks like heart attacks and if such a risk is greater than that from other therapies.
Questioning Role
The panel was also asked to consider whether the drug should continue to be sold in the U.S. If the panel rules the drug should stay on the market, the agency wants to know what steps it can take, such as limitations on Avandia’s use, to maximize its benefit while reducing its risk.
“If this drug really does increase the risk of heart attack by 20 or 30 or 40 percent, we really should question its role,'’ said an FDA official, who declined to be named, in a telephone briefing with reporters last week. “We’re asking the committee, do the data tell us that or not?'’
Graham, in his slides, said a similar drug called Actos from Osaka-based Takeda Pharmaceutical Co. doesn’t have the same cardiovascular risks.
A Takeda study comparing Actos to Avandia found patients on Actos had a 22 percent lower risk of heart attacks. The report, expected to be discussed at the advisory committee hearing today, comes from an analysis of a medical claims database including 30,000 diabetics treated from 2003 to 2006.
Higher Risk
Patients taking Avandia had as much as a 3.5-fold increased risk of heart attacks and related complications compared with patients taking Actos in studies analyzed by the FDA, according to Graham’s slides. In addition, Avandia offers no unique advantages and isn’t as good with other outcomes, such as controlling cholesterol levels, he said.
An estimated 246 million people, nearly 6 percent of the world’s adult population, suffer from diabetes and 3.8 million a year die from it, according to the International Diabetes Federation. The most common form is type 2, linked to a sedentary lifestyle and excess weight.
The cells of those patients don’t properly produce and use insulin, the hormone that coverts blood sugar to energy. The disease is progressive, with patients needing more and more aggressive therapy to get their blood sugar under control. Persistently high levels eventually damage the nerves and blood vessels, leading to blindness, kidney failure and death.
Sensitive to Insulin
Avandia and other treatments make the cells more sensitive to the insulin the body produces. Other therapies prompt the body to make more insulin. Eventually, most patients need insulin injections to control their blood sugar.
The advisory committee’s position will help determine whether and to what extent Avandia will contribute to Glaxo’s future earnings. It was the world’s best-selling diabetes pill and London-based Glaxo’s second-biggest drug last year, bringing in $3.3 billion for the company.
After the heart-attack risk was reported in May, Avandia sales fell 22 percent in the second quarter as doctors turned to Actos, a similar drug from Osaka-based Takeda Pharmaceutical Co., and newer medications from Merck & Co. and Eli Lilly & Co.
Before the controversy began, analysts were expecting Avandia to reach peak sales of about $6 billion (3 billion pounds) by 2011. Now many say the chances are slim.
“It will be very difficult to recover from this,'’ Nick Turner, an analyst at Mirabaud Securities in London, said in a telephone interview earlier this month. “Even if the FDA doesn’t can it, it is going to be hard to get patients to take the risk,'’ he said. “Every man and his dog is going to be looking at every trial for heart risk.'’
To contact the reporters on this story: Justin Blum in Washington at jblum4@bloomberg.net ; Michelle Fay Cortez in Minneapolis at mcortez@bloomberg.net