Avandia

What is Avandia?

Rosiglitazone, marketed as Avandia, was approved by the Food and Drug Agency (FDA) for treatment of type II diabetes on May 25, 1999. Diabetic patients are at increased risk of heart attack and stroke. Maintaining lower blood sugar levels is believed to prevent diabetes long-term complications including cardiovascular disease and heart attacks. Avandia was approved based on its ability to lower the blood sugar level in diabetic patients. Avandia was developed and marketed by the U.K. drug giant, GlaxoSmithKline (GSK) and soon became GSK’s second best selling drug. In 2006 alone, U.S. patients filled 11 million prescriptions for the drug which earned GSK over $3 billion.

Avandia Problems Come to Light.

In May 2007, an article published in the New England Journal of Medicine raised serious questions about the safety of Avandia. The article reported the results of statistical analysis of adverse cardiovascular effects of this drug by the renowned heart scientist, Dr. Steven Nissen, Chairman of the Department of Cardiovascular Medicine at the Cleveland Clinic.  According to the article, Avandia caused a 43% increase in heart attack (myocardial infarction) and a 64% increase in cardiovascular-related death in patients taking the drug.

Dr. Nissen’s conclusions were based on a “meta” analysis, i.e., a statistical analysis which combined data from all relevant clinical trials of Avandia completed to date. Information from 42 clinical trials of Avandia was used in Dr. Nissen’s statistical analysis. Based on the requirements of the FDA and the regulatory agencies in the Europe, GSK had performed a number of pre- and post-marketing of clinical and observational trials on Avandia. However, only the results of two major GSK-sponsored pre-marketing clinical trials were published by GSK. GSK neither published, nor reported to the FDA the results of many of the post-marketing trials of the drug.

GSK Knew of the Problems.

Evidence shows that GSK was aware of this problem all along. As early as 1999, Dr. John Buse, a professor of medicine at the University of North Carolina and the 2007-2008 President of the American Diabetes Association suggested that Avandia may cause increased cardiovascular risks. His conclusion was based on the evidence that the drug had negative effects on fats in the blood and on the emergence of signals that it increased the risk of heart attack.

GSK Threatened and Silenced Avandia Critics.

GSK responded to Dr. Buse’s warnings by engaging in a concerted effort to intimidate and silence him.  Dr. Buse was threatened with being sued  for a loss in market share and loss of profits. As a result of all that pressure, Dr. Buse was forced to sign some legal document in which he agreed not to discuss this issue further in public. He was also forced to write a “retraction letter.” However, evidence shows that the letter was not written by Dr. Buse.  The letter was prepared by GSK and Dr. Buse simply signed it.

Dr. Nissen’s article prompted a Congressional investigation in June 2007. The Senate Finance Committee concluded that based on an analysis by FDA scientists an estimated 83,000 excess heart attacks were caused by Avandia since coming on the market. According to this report, “had GSK considered Avandia’s increased cardiovascular risk more seriously when the issue was first raised in 1999 by Dr. Buse, instead of trying to smother an independent medical opinion, some of these heart attacks may have been avoided.”

Dr. Buse was not the only endocrinologist raising early questions about Avandia. Dr. Anne E. Peters, a diabetes specialist who runs a clinic for Los Angeles County and is affiliated with the medical school at the University of Southern California, became concerned with the cardiovascular safety of Avandia five years ago. As a result, she removed Avandia from the list of preferred drugs maintained by the Los Angeles Clinic. GSK’s approach towards her was different. In her case, GSK resorted to bribery. According to Dr. Peters, “The Avandia people, it was just so surprising, they asked me what I wanted to keep Avandia on the formulary.” She asked GSK to establish a database at the clinic that would track the outcomes of patients on Avandia and another diabetes drug (Actose). However, according to Dr. Peters, “they wanted to give me everything but approve my request.” GSK never established the database.

Nissen’s Results Were Confirmed by Other Studies.

Despite GSK’s efforts to refute Dr. Nissen’s conclusions, they have since been confirmed by other studies. In a paper published in Journal of the American Medical association (JAMA), scientists from Wake Forest University School of Medicine analyzed four clinical trials of Avandia lasting at least one year. They found that patients taking Avandia had a 42% greater risk of having a heart attack than those in the control group.[1] Similarly, studies by a group of German scientists, from the Düsseldorf’s Heinrich-Heine University, concluded that Avandia could actually worsen complications of diabetes.[2]

Black Box Warning

On July 30, 2007, the FDA held a Joint Meeting of the FDA Endocrinologic and Metabolic Drugs Advisory Committee and the Drug Safety Management Advisory Committee to discuss the issue. Committee members decided that available data support the conclusion that Avandia increases the risk of cardiac ischemia (heart attack) in type 2 diabetic patients. While they ultimately voted against removal of Avandia from the market, they emphasized the need for strengthening the label language (Black Box), more studies by the manufacturer, and educating doctors and patients regarding the risks of Avandia. Black Box is the highest form of warning that FDA issues in regard to a drug. In November 2007 FDA ordered GSK to add a black box warning to Avandia packaging.

Conclusion

Cardiovascular disease is the number one cause of morbidity and mortality in diabetic patients. While lowering a diabetic person’s blood sugar level is a desirable outcome, any diabetes medicine is ultimately prescribed for reducing the risk of diabetic complications such as cardiovascular disease and heart attacks. A drug such as Avandia, that would itself increase the chances of those complications, poses an entirely unacceptable risk to the safety and wellbeing of diabetic patients. It is unconscionable for a drug company to knowingly market and promote such drug.

GSK was aware of all the dangers that Avandia posed to diabetic patients. But in a cold-blooded cost/benefit analysis, it chose to ignore and conceal them. By hiding what it knew would damage the commercial prospects of Avandia, GSK recklessly placed the lives of those treated with Avandia in a danger that they should not have been exposed to. GSK’s conduct was simply unconscionable.

What Can Our Law Firm Do for You?

Our law firm is actively participating in Avandia litigation. The cases involving Avandia are now followed at a national level by a Plaintiff Steering Committee (PSC).  Our lawyers are among a select group of lawyers directing the Avandia litigation on the national level. Moreover, one of our lawyers, Dr. Tara Tabatabaie, is a former scientist and diabetes researcher who is now a member of the PSC and closely involved with the medical and scientific aspects of the case.

If you or a loved one have been harmed by consuming Avandia, contact our law firm. We are ready to help you pursue your legal rights against the maker of this drug that knowingly put this dangerous drug on the market.