Most of the 26-member advisory FDA panel voted to loosen the restrictions which were placed on GSK’s diabetes drug Avandia (rosiglitazone) in 2010 because of concerns it might raise the risk of heart attacks and death from cardiovascular causes.

Seven panel members voted to remove all the restrictions, stating that the evidence for heart attack risk was not compelling, while five voted to leave the restrictions as they are. Thirteen voted to loosen the restrictions, e.g. not requiring patients to sign an informed consent form or to register.

Just one panelist, Ida Spruill, voted to ban Avandia. Spruill, who says she has diabetes, and once took Avandia. As a nurse, she says she would not be comfortable prescribing Avandia to her family members or other patients.

In 2011, severe restrictions were placed on Avandia by the FDA, including forcing physicians and patients to register and complete consent forms so that it was clear they were aware of the risks. Since those restrictions were implemented, the drug can only be dispensed through mail order to patients on the registry from specially certified pharmacies.

These restrictions were the kiss of death for what was at the time a very lucrative medication for GSK (GlaxoSmithKline). From January 2010 to the end of October 2010, 460,500 patients had filled a prescription for a rosiglitazone product from outpatient retail pharmacies – eventually the number dropped to 3,000.

The European Medicines Agency had already suspended the use of rosiglitazone in 2010.

Forbes today quotes a patient who is also panel member, Rebecca Killion, as saying “Our charge is to be safe, but to be sane.

Dr. Steven Nissen, one of the initial doctors to raise concerns about Avandia six years ago, said he was fairly satisfied with the FDA-panel’s recommendation. While he admits that he is not happy with a single patient getting the medication, the fact that a total lifting of all restrictions seems unlikely means that Avandia “will not be appearing in pharmacies around the corner”.

It is doubtful that the panel’s recommendation will have any impact on GSK’s actions or sales. If it is eventually found conclusively that Avandia is not linked to heart attack risk, it will likely remain a small player in the huge diabetes pharmaceuticals market. Experts doubt GSK will raise Avandia’s price, as is sometimes done by drugmakers for small market medications.

According to Forbes, the FDA may have stacked the deck regarding individual panel members this time round. It appears that those who voted against Avandia in 2010 were either not invited, told they were not invited because of a conflict of interest, or invited in a half-hearted way, i.e. no huge effort was made by the FDA to make sure the opposers came.

Glaxo said that the panel’s discussion overall reflected confidence in RECORD’s integrity and reliability. The original findings of RECORD showed that the risks of mortality and major adverse cardiac events with Avandia together with metformin or SU were no different than with a combination of metformin and SU (without Avandia), according to an independent re-examination carried out by the Duke Clinical Research Institute.

Dr. James Shannon, GSK’s Chief Medical Officer, said:

“We appreciate the committee’s thorough examination of the RECORD results and will continue to work with the FDA as it considers the recommendation of the committee. We continue to believe that Avandia is a safe and effective treatment option for type 2 diabetes when used for the appropriate patient and in accordance with labelling.”

The recommendations of the Endocrinologic and Metabolic Drugs Advisory Committee and the Drug Safety and Risk Management Advisory Committee will be taken into account when the FDA makes its final decision on Avandia. The FDA usually goes along with an advisory committee’s recommendation, but it is free to decide differently.

A 2007 article in NEJM (New England Journal of Medicine) titled “Effect of Rosiglitazone on the Risk of Myocardial Infarction and Death from Cardiovascular Causes”, found that oral agent rosiglitazone (Avandia) used to treat type 2 diabetes might be linked to a higher risk of heart attack and death from cardiovascular causes.

The American Heart Association, American Diabetes Association and the American College of Cardiology responded immediately saying the rosiglitazone study deserved serious thought and follow-up. The three organizations, after reviewing the study, described the risk associated with rosiglitazone as “small, but nonetheless one that must be considered carefully”. Patients were advised to talk to their doctor to determine the most appropriate course of action. They were urged not to stop taking Avandia without talking to their physician first.

This was followed by several more studies which drew the attention of regulatory authorities around the world.

Written by Christian Nordqvist