FDA Restricts Access to Avandia

Citing heart risks, agency also orders review of key research on cardiovascular impact; European regulators suspend drug's sales

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By Steven Reinberg
HealthDay Reporter

THURSDAY, Sept. 23 (HealthDay News) -- In response to major concerns about heart risks, U.S. health officials on Thursday severely restricted use of the diabetes drug rosiglitazone (Avandia) to patients with type 2 diabetes who cannot control their disease on other medications.

U.S. Food and Drug Administration officials also ordered the drug's manufacturer, GlaxoSmithKline, to get an independent review of a key company-run trial of the drug's heart effects. And they pulled the plug on another company-run trial comparing Avandia to its competitor, pioglitazone (Actos).

"Because of concerns about cardiovascular safety, FDA is announcing regulatory action on medications containing rosiglitazone," FDA Commissioner Dr. Margaret A. Hamburg said during a morning press conference. "FDA is significantly restricting the use of these products by requiring the manufacturer to submit a Risk Evaluation and Mitigation Strategy [REMS]."

The FDA is requiring GlaxoSmithKline to develop a program that will restrict access to the drug to those patients for whom other treatments have not worked.

In addition, doctors will have to state and document a patient's eligibility to use Avandia. They will also have to tell patients about the cardiovascular safety risks associated with Avandia, and patients will have to acknowledge that they understand those risks.

Those currently using Avandia will be allowed to continue taking the drug, Hamburg said. However, once the REMS is in place these patients will also have to have their doctors justify use of the drug.

FDA officials believe this program will significantly reduce the number of people taking Avandia.

According to the agency, there was not enough evidence of Avandia's cardiovascular risks to pull the drug from the market, which is why it opted to restrict its use instead.

But in Europe, the European Medicines Agency has suspended marketing of the drug, forcing patients to find another drug to control their blood sugar. The suspension will remain in place unless there is new data showing that the benefits of the drug outweigh its risks.

Avandia is also sold in combination with other diabetes drugs, with metformin under the brand name Avandamet or with glimepiride under the brand name Avandaryl, the FDA noted.

Avandia belongs to a class of drugs known as thiazolidinediones and is intended to be used along with diet and exercise to control blood sugar in patients with type 2 diabetes.

The FDA has also ordered GlaxoSmithKline to form an independent group of scientists to review the company's clinical trial known as RECORD, which studied the cardiovascular safety of Avandia compared with standard diabetes drugs. During the agency's review of the trial, questions came up about bias in identifying cardiovascular events.

"We believe this review will provide additional clarity about this trial and the safety of rosiglitazone," Hamburg said.

As published, the RECORD trial did not show any cardiovascular risk from Avandia, Dr. Janet Woodock, director of the FDA's Center for Drug Evaluation and Research, said during the press conference.

However, "at this time we cannot rely on these results," Woodock said.

In addition, the FDA stopped the company's current trial, called TIDE. This trial compares Avandia with Actos and with standard diabetes drugs. "This study does not meet the criteria for safety studies at this time," Hamburg said.

After the review of the RECORD trial is completed, the FDA may choose to take additional action, officials said.

Dr. Ellen Strahlman, GlaxoSmithKline's chief medical officer, said in a statement that "our primary concern continues to be patients with type 2 diabetes and we are making every effort to ensure that physicians in Europe and the U.S. have all the information they need to help them understand how these regulatory decisions affect them and their patients."

According to the company, worldwide sales of Avandia in the first half of 2010 totaled $500 million. In the United States, about 600,000 people are currently taking Avandia, Hamburg said.

Dr. Ronald Goldberg, a professor at the Diabetes Research Institute of the University of Miami Miller School of Medicine, said that "given all the evidence pointing to risk, even though it's not conclusive by any stretch of the imagination, it rises to a level to warrant restricting its [Avandia's] use."