More than one dozen cases of liver failure and death were reported in patients taking GlaxoSmithKline Plc’s Avandia (rosiglitazone), advocacy group Public Citizen said on Thursday in a petition calling for a ban of the drug. But GlaxoSmithKline defended its drug, saying its own review by an independent panel earlier this year said the liver risks were acceptable.
"We do not believe there is a connection between liver toxicity and this medicine," the company said in a statement, adding it had not yet read the group’s petition.
The safety of patients using our medicine is very important to us. On a continual basis, an external Hepatic Safety Board reviews any adverse event report received by GSK of liver failure, liver-related deaths and liver transplants for possible relationship to AVANDIA. As recently as July 2008, this panel of experts continued to endorse a favorable hepatic safety profile for AVANDIA. Patients being treated with AVANDIA or other medicines to control blood sugar levels should remain on therapy, unless their doctor advises a different course of action. AVANDIA has been shown to be a safe and highly effective treatment for type 2 diabetes for the appropriate patient. GSK strongly supports the safety and efficacy of AVANDIA based on extensive clinical trial experience and widespread post-marketing use. The record of safety and effectiveness of AVANDIA is backed by one of the largest clinical trial programs (including 52,000 patients) ever undertaken for any medicine.
Data from long-term clinical trials, which offer the most rigorous scientific measurement of safety and efficacy, provide substantial evidence to assess the benefit-risk of AVANDIA in treating patients with diabetes. Importantly, the Public Citizen petition did not include data from the current Prescribing Information for AVANDIA regarding ADOPT (A Diabetes Outcomes Progression Trial). ADOPT, the largest head-to-head diabetes trial, showed that AVANDIA sustained glycemic control longer than metformin or sulfonylurea, for up to five years. Additionally, outcomes from five long-term clinical studies did not demonstrate an increased risk of total mortality for AVANDIA compared to other commonly used oral diabetes medicines on the market. The current FDA-approved label for AVANDIA states that the available data are inconclusive on the risk of myocardial ischemia.
Public Citizen said its review of U.S. Food and Drug Administration data found 14 previously unpublished cases of severe drug-induced liver failure, including 12 deaths.
That risk, coupled with other known complications that include heart failure, fractures and vision loss, was too great to allow the drug to continue to be sold in the United States, especially with other treatments available, it said in a petition to the FDA.
"The evidence for this unique combination of toxicities is compounded by the accompanying lack of evidence of any clinical benefit, compared to other approved drugs for diabetes," the petition said.
Sales of Avandia have plunged in the past year after the heart risk surfaced in an analysis of available clinical studies.
Since then, experts at two major diabetes associations have withdrawn their support of the drug, instead backing lifestyle changes such as diet and exercise as well as other treatments.
Still, Public Citizen estimated about 10,000 prescriptions continue to be filled each day. "Thus, it is urgent for the FDA to immediately ban rosiglitazone," it said.
Representatives for the FDA did not immediately return requests for comment.
Prescribing Information at www.AVANDIA.com