In Comparison, Europe's Regulators Had Glaxo Change Avandia Label In 2006 To Include Warning About Risk Of Cardiac Ischemic Events Such As Heart Attacks
(Posted by Tom Lamb at DrugInjuryWatch.com)
In a May 24, 2007 New York Times (NYT) article about Avandia, Stephanie Sauls and Gardiner Harris reported the FDA was put on notice as far back as 2000 that there was concern in parts of the medical community about the cardiovascular safety of Avandia, a diabetes drug from GlaxoSmithKline.
Most U.S. doctors and patients, however, were left in the dark regarding serious heart problems associated with Avandia until the May 21, 2007 early online publication by the New England Journal of Medicine (NEJM) of an article by Steven Nissen and Kathy Wolski about a new Avandia meta-analysis.
From the the Sauls and Harris May 24 NYT article we learned what the FDA knew in 2000:
A leading diabetes doctor sent the Food and Drug Administration a letter seven years ago that warned of the heart risks of the drug Avandia....
The letter in 2000 to the F.D.A. was written by Dr. John B. Buse, chief of endocrinology at the University of North Carolina in Chapel Hill, who is about to become the president of the American Diabetes Association. [Dr. Buse's] letter from seven years ago sounded an alarm about Avandia, citing "a worrisome trend in cardiovascular deaths and severe adverse events" among patients using the drug.
So, despite all the recent attention created by the NEJM publishing this May 2007 Avandia article, it turns out that this is old news to the FDA, which has seen fit to take no action regarding the cardiovascular problems related to GlaxoSmithKline's diabetes drug.
Moreover, it appears that the FDA is going along with GlaxoSmithKline's suggestion that the agency wait until 2009 for an answer to the Avandia drug safety questions raised by the Nissen and Wolski's NEJM Avandia meta-analysis article.
In more detail, Glaxo seems to be telling the FDA that the agency should wait to take any action until Glaxo can present the results of RECORD, a phase III clinical trial designed specifically to determine the extent of cardiovascular risk associated with Avandia in the patient population for which Avandia is intended. RECORD is a large, long-term clinical trial that Glaxo started in 2000 and is still conducting to date. Besides wondering why such a study had not done before the FDA approved Avandia, the more pressing problem is that this Glaxo-sponsored study of Avandia will be completed no earlier than 2009 according to the drug company.
Meanwhile, here is the history of Avandia regulatory actions taken by EMEA, the European Union (EU) counterpart of the FDA, as set forth in the EMEA's May 23, 2007 press release regarding the NEJM Avandia article by Nissen and Wolski:
When [Avandia] was first authorised in the EU in 2000, it was contraindicated in patients with a history of cardiac failure. Since then, the European Medicines Agency's Committee for Medicinal Products for Human Use (CHMP) has kept [Avandia] under close surveillance for cardiovascular effects (cardiac failure and other cardiac disorders including myocardial infarction). The majority of the studies included in the NEJM paper have already been assessed by the CHMP. The EU product information was updated in September 2006 with information about the risk of cardiac ischaemic events.
If you are interested in what the EMEA has done as regards Avandia, take a look at the European Public Assessment Report for Avandia and the current EMEA-approved product information for Avandia.
P.S. In his blog, Eye on FDA, Mark Senak compares and contrasts the differences between the May 21 safety alert issued by the FDA on Avandia and the May 23 EMEA statement on Avandia safety. (5/25/07)
P.S. According to The Washington Post, on May 24, 2007 Senator Charles Grassley made a floor statement about Avandia that was placed in the Senate record, in which he "complained that FDA higher-ups have said they want to wait for results of an ongoing study that will not be available for two more years before making a decision." (5/25/07)