Avandia Heart Risks News

Recall or Reassurance On Safety of Avandia?

- RTT News

07/06/2010 - The count down to the re-review of GlaxoSmithKline plc's controversial diabetes pill Avandia has begun!

At a 2-day meeting - July 13 and July 14, two of FDA's advisory committees are scheduled to review the safety issues of Avandia for the second time, focusing primarily on the cardiovascular safety of the drug. Avandia was first approved in 1999 for use as a monotherapy and in combination with metformin for blood glucose control in adults with type 2 diabetes mellitus. In 2003, Avandia was approved for use in combination with insulin for the treatment of type 2 diabetes.

The controversy on Rosiglitazone, better known Avandia, started in May 2007 following publication of a meta-analysis study by Cleveland Clinic cardiologist Steven Nissen and statistician Kathy Wolski in the New England Journal of Medicine.

... So what is the hubbub about Avandia, which is still a blockbuster?

In May 2007, the New England Journal of Medicine reported that there was a significant increase in the risk of heart attack and other fatal cardiovascular events due to the use of Avandia by those with type 2 diabetes. The study was a compilation of data from 42 different already completed Avandia studies available from publicly disclosed summaries of events.

The controversy surrounding Avandia led to convening an FDA panel meeting to discuss the potential risks of the drug in July 2007. Though the panel voted 20-3 that Avandia did increase the risk of heart attacks, it subsequently voted 22-1 in favor of Avandia remaining on the market, pending a review of additional data.

On October 2, 2007, the FDA's Drug Safety Oversight Board voted very narrowly 8-7 to keep Avandia on the market, and in the following month, the FDA added a black box warning - the strongest safety warning, to the drug about potential increased risk for heart attacks.

With the FDA concluding that there wasn't enough evidence then to indicate that the risks of heart attacks or death are different between Avandia and some other oral type 2 diabetes treatments, GlaxoSmithKline was requested to conduct a new long-term study to evaluate the potential cardiovascular risk of Avandia, compared to an active control agent.

Accordingly, Avandia is being studied in a double-blind company-sponsored trial dubbed TIDE, in which the drug is directly compared to its rival drug Actos made by Takeda Pharmaceuticals. The trial is expected to be completed in 2015.

In February of this year, the U.S. Senate Committee on Finance released a report based on a two-year inquiry of Avandia. According to the report, GlaxoSmithKline was aware of the possible cardiac risks associated with Avandia years before such evidence became public. The Senate report also alleges that the company intimidated independent physicians, focused on strategies to minimize findings that Avandia may increase cardiovascular risk, and sought ways to downplay findings that the rival drug Actos might reduce cardiovascular risk.
The report has also pointed out that two FDA safety officials - David Graham and Kate Gelperin, in an October 2008 memo have written that there is no evidence that Avandia confers any unique health benefits over Actos while there is strong evidence that Avandia confers an increased risk of heart attacks and heart failure compared to Actos.

However, GlaxoSmithKline has rejected the conclusions of the Staff Report of the Senate Committee on Finance and continues to assert that the safety and effectiveness of Avandia is well characterized in the label approved by the FDA.
Meanwhile in August 2009, data from a large, long-term clinical trial called the RECORD (Rosiglitazone Evaluated for Cardiovascular Outcomes and Regulation of Glycemia in Diabetes) study were submitted to the FDA by GlaxoSmithKline. The RECORD study is designed to evaluate the cardiovascular safety of Avandia.

The FDA will present the totality of new and existing cardiovascular safety data on Avandia after completing its review of the data from the RECORD study, and also provide an updated assessment of the risks and benefits of the drug at the joint public meeting of the Endocrinologic and Metabolic Drugs and Drug Safety and Risk Management Advisory Committees to be held July 13 and July 14.

In addition to the RECORD trial data, observational data and health claims data specific to Avandia, as well as meta-analysis of several trials of Actos will be presented at the joint meeting.

Avandia was GlaxoSmithKline's second-best selling drug in 2006. The sales of the drug have been on the decline since 2007 following publicity around questions regarding risks associated with the product.

The global sales of Avandia, which were £1.39 billion in 2006, dropped to £1.22 billion in 2007, £805 million in 2008 and further plummeted to £771 million (US$1.17 billion) in 2009. In the first quarter of fiscal 2010, Avandia product sales dropped to £169 million from £197 million in the comparable year-ago quarter.

According to reports, over 13,000 product liability lawsuits related to Avandia have been filed against GlaxoSmithKline. The lawsuits filed against the company allege negligence, fraud, breach of warranty and a failure to warn about the risks of the diabetes drug. GlaxoSmithKline has reportedly settled close to half of the Avandia lawsuits.

With growing concerns about Avandia's safety profile, last month, Germany's drug watchdog - the G-BA, reportedly directed health insurers in that country to discontinue reimbursement of Avandia.
Even though GlaxoSmithKline stands firmly behind the safety of Avandia, the controversy surrounding the drug has only escalated over the years.

Avandia Side Effects Cases Still Being Accepted: