The United States and Europe are both greatly restricting use of the diabetes drug Avandia, culminating several years of concern that the drug increases
the risk of heart problems. The European Medicines Agency (EMA)
is taking Avandia off the market, while the U.S. Food and Drug Administration (FDA) is placing the drug in a
special high-risk category that is likely to drastically cut its use.
Both agencies had access to the same Avandia data, which was compelling but also incomplete. The conclusion that Avandia causes heart attacks and other
cardiac issues came from combining data from many different clinical trials, a method that's less powerful statistically than individual trials
designed to answer such questions. "My job would be infinitely easier if we had consensus and scientific clarity on this issue," said Margaret Hamburg,
FDA's commissioner, in a press conference this morning. But she concluded the evidence justified significant restrictions.
Most frustrating to regulators, a large clinical trial specifically requested by European regulators to address risks, called RECORD, has come under fire for failing to properly assess
cardiac events. FDA officials said today that their next step will be to have the company that makes Avandia, GlaxoSmithKline, set up an independent
review panel to reassess all potential cardiac issues that surfaced in RECORD patients.
In the meantime, Avandia will become a lot harder to get. FDA has placed it under a special program it runs called Risk Evaluation and Mitigation
Strategies. REMS is designed to ensure that the benefits of potentially risky drugs continue to outweigh the hazards for every patient taking them. The
program currently includes drugs such as the acne medication Accutane, which causes birth defects. FDA has also halted a Glaxo trial that aimed to
compare Avandia with another drug used by diabetics, Actos, which is considered safer. FDA had suspended the trial in the summer.
In Avandia's case, patients who wish to continue using it will have to sign a document acknowledging that they understand the drug's risks. New
patients will be eligible to take it only if doctors certify that other treatments haven't brought the patients' blood sugar under control and that
they cannot take Actos for medical reasons. "We believe this action will considerably limit the number of people who are on [Avandia]," said Janet
Woodcock, director of the Center for Drug Evaluation and Research in Silver Spring, Maryland.
For European regulators, limiting Avandia's use was deemed insufficient, and within a few months Avandia will no longer be available in most European
countries. "The accumulated data support an increased cardiovascular risk of rosiglizatone," the generic name for Avandia, said EMA in a statement.
"The benefits of rosiglitazone no longer outweigh its risks." But Woodcock noted there was still "considerable uncertainty about the magnitude and the
existence of this cardiovascular risk." She is hopeful that reassessing RECORD will help.
)
)
