GlaxoSmithKline: Avandia unlikely to recover despite panel decision

FDA advisory committees have voted to keep GlaxoSmithKline’s Avandia on the market.

The debate over the safety of GlaxoSmithKline’s Avandia following the publication of a meta-analysis which linked the diabetes drug with adverse cardiovascular events may finally be drawing to a close with an FDA advisory panel’s recommendation to keep the drug on the market. However, the episode has called into question the FDA’s handling of the situation and damaged GSK’s sales of the drug.

The FDA’s joint meeting of the Endocrinologic and Metabolic Drugs Advisory Committee and the Drug Safety and Risk Management Advisory Committee voted 22 members to one in favor of keeping Avandia on the market, albeit with warning labels and stricter standards of use.

The meeting was prompted by the controversial publication in The New England Journal of Medicine of a meta-analysis of 42 clinical studies by Dr Nissen, showing an association between Avandia and increased risk of myocardial infarction and death from cardiovascular causes. This publication, in addition to Adandia’s other well known side-effects such as fluid retention and bone fractures, has generated huge media interest.

As a result, many diabetes specialists and GPs have stopped prescribing Avandia to their new patients and started switching their existing Avandia patients to other drugs, leading to a significant drop in GSK’s Avandia sales. GSK reported a drop in new prescriptions by 42% and sales of Avandia in the US by 22%.

Looking at bigger picture, there are a few questions that have been posed to the medical community: can the FDA or any other authority make a decision on safety of a drug based on a meta-analysis vs. hard data? Observing the speed with which the meta-analysis was published by the NEJM, without informing FDA and GSK, was there really a mix of science and politics?

In the circumstances, the panel’s decision was correct. Given the current lack of hard data it would be unjustifiable to make a decision on whether Avandia’s risks outweigh its benefits based on the meta-analysis. The committee acknowledged the fact that although there may be cardiovascular risks associated with Avandia, it is for trusted physicians to make the final call.

However, the commercial damage to Avandia has already been done and despite GSK’s confidence that its ongoing trial RECORD will bring clarification and hard data evidence to confirm the safety of the drug, this drug is not expected to recover well. Instead, Datamonitor expects Avandia to slowly fade out of the market over the next five years, in which period it will be significantly affected by key patent expiries within the TZD class, and by the introduction of new antidiabetic agents.