In a move that many anticipated, the FDA is leaving the controversial Avandia diabetes pill on the market, but with restrictions for patients who are unable to control their illness by using other meds. In astatement, FDA commish Margaret Hamburg says the step is an effort to "strike the right balance to support clinical care.”
Want to know about the agency thinking behind this decision? You can read recommendations from several FDA officials right here. UPDATE: And you can read an editorial just published by Hamburg, FDA deputy commish Josh Sharfstein and Janet Woodcock, who heads the FDA's Center for Drug Evaluation & Research, in the New England Journal of Medicine.
At the same time, though, the European Medicines Agency is suspending use of Avandia (here is the statement), but not revoking approval. Hamburg says there was coordination, but the FDA conducted analysis of raw data, while the EMA does not. The difference in regulatory action is based on "different regulatory tools" (read a Q&A from the EMA here).
GlaxoSmithKline, which has been criticized for failing to sufficiently disclose clinical trial data about cardiovascular risks, is being required to create a restricted access program under a risk evaluation and mitigation strategy (there are, by the way, about 30 drugs with a REMS requirement). From now on, Avandia will only be available to new patients if they can't use other meds, including the rival Actos pill. Doctors will have to document patient eligibility; patients will have to review statements describing CV safety concerns associated with Avandia and acknowledge they understand the risks. There are no restrictions on existing Avandia patients. About 600,000 people currently use Avandia in the US and, of course, this will drop very soon.
Meanwhile, the FDA ordered Glaxo to convene an independent group of scientists to review key aspects of its RECORD clinical trial, which studied Avandia's CV risks compared to other diabetes drugs. During the course of the FDA’s review of the RECORD study, the FDA says with understatement that "important questions" arose about potential bias in identifying CV events and so the FDA wants an independent review to provide additional clarity about the findings (back story). Woodcock says the results were "unreliable." And in remarks with the media she adds: "We still have considerable uncertainty about the magnitude of CV risk and the next step...is to readjudicate the study, which directly addresses this risk."
The FDA also halted the TIDE clinical trial and rescinded all of the regulatory deadlines for completion of the trial. The TIDE trial compares Avandia to Actos and to standard diabetes drugs. There had been criticism over the ethics of running such a trial because Avandia is known to have greater CV risks than the Takeda Pharmaceuticals pill. Hamburg says a key reason for stopping the TIDE trial is that it does not meet the critieria set by the Institute of Medicine, which reviewed the ethics issue (see here).
As for Glaxo, the drugmaker will halt all promotion of Avandia. And here's a statement from Ellen Strahlman, Glaxo's chief medical officer. The controversy, by the way, has caused Avandia sales to drop in the first half of 2010 by 18 percent to about $504 million worldwide. In the US, sales fell 23 percent to $258 million and in Europe, sales dropped 17 percent to $113 million. With the regulatory moves, global sales are forecast to be in the range of $157 million to $232 million in the second half of this year (here is the Glaxo statement). And last but not least, Glaxo is certain to face more lawsuits after recently taking a $2.4 billion charge to cover, in part, Avandia litigation (back story).