Poor Toyota.  The car maker has been forced to recall more than 8 million vehicles worldwide after news that at least 34 deaths have been linked to Toyota vehicle problems going back as far as 2004. But compare those 34 deaths with the more than 1,000 reports of patient deaths linked with the prescription drug Avandia in just one nine-month period last year, a death rate described by an Institute for Safe Medication Practices report as: “more than any other drug we monitor.” John Mack, editor of Pharma Marketing News, warns:

“If people are afraid to buy Toyotas, then based on average yearly death rates, they should be about 400 times more afraid to take Avandia.”  

Avandia (which is the brand name for the Type 2 diabetes drug rosiglitazone, manufatured by drug giant GlaxoSmithKline) was once taken by millions worldwide, but that changed after a Cleveland Clinic study released in early May of 2007 suggested that Avandia increased a user’s odds of heart attack by 43%. At the time, Dr. Bruce M. Psaty of the University of Washington – who also co-wrote an accompanying editorial in the New England Journal of Medicine – urged the Food & Drug Agency to restrict access to Avandia, and then cited both the agency and GlaxoSmithKline for poor oversight.

“The primary problem here is that studies that were needed early on about the health benefits of Avandia were never done.”

For a graphic illustration of how GSK simply distorted their study numbers, check out this AdWatch analysis of an Australian Avandia ad.

Here in Canada, GlaxoSmithKline was ordered to update prescribing warning information on product labels for all drugs made from or containing the drug rosiglitazone: Avandia, Avandamet and AvandarylTM.  In the U.S., a ‘black box’ warning label was ordered for product packaging that advised consumers about potential cardiac damage.

Then in 2008, Dr. David Graham and Dr. Kate Gelperin, drug safety officials at the FDA, claimed that Avandia was directly responsible for at least 500 additional heart attacks every month, and warned:

“Rosiglitazone should be removed from the market.”

* see News Reports below

Despite that strong language, annual sales of the blockbuster drug Avandia still topped $1.2 billion last year. Somebody is still prescribing this drug to patients, despite fierce attacks from researchers, scientists, the FDA itself, and now  a scathing 2-year investigative report released last week by the U.S. Senate.

Is it just me, or do others wonder why this drug, in light of increasingly damning evidence, is still allowed on the market?   Are 500 additional heart attacks every month not enough reason to pull Avandia?  How come we are able to quickly pull millions of Toyotas off the road, but we can’t seem to get a drug that may be responsible for thousands of heart attacks and deaths off your doctor’s Rx pad?

And what about those disclosures this week from BNet Media that the American Heart Association – which released a strangely non-committal “inconclusive’ 11-page response to the Senate investigators – had failed to reveal that the non-profit had received over $3.6 million in donations from GlaxoSmithKline over the past four years? How handy for GSK.

GlaxoSmithKline, meanwhile is on an all-out defensive. In a statement by spokesperson Mary Anne Rhyne, the drug company said it rejects conclusions that Avandia is risky for patients.

According to a recent report in Business Week, it seems that executives of London-based Glaxo had obtained a copy of the original 2007 New England Journal of Medicine study in advance of its publication. They got this from a company consultant who coincidentally also worked as a reviewer for the journal. Again, how remarkably handy for GSK.

Although company scientists internally recognized the study’s validity and acknowledged Avandia’s heart risks, Glaxo prepared a public relations effort to refute suggestions that the drug triggered heart attacks, according to internal e-mails reviewed by Senate researchers cited in the report. U.S. Senators Baucus and Grassley wrote in their Senate committee report:

“It can be argued that GSK had a duty to warn patients and the FDA of the company’s concerns.

“Instead, GlaxoSmithKline executives attempted to intimidate independent physicians, focused on strategies to minimize or misrepresent findings that Avandia may increase cardiovascular risk, and sought ways to downplay findings that a competing drug might reduce cardiovascular risk.”

A revealing study presented at the American College of Preventive Medicine annual meeting by Dr. Mohammed Hassan Murad of Mayo Clinic reviewed 202 published medical journal articles that addressed the possible association between heart attack risk and Avandia in diabetes patients.

Among journal article authors who concluded Avandia does NOT increase the risk, 86% had financial relationships with GlaxoSmithKline. Among authors of articles offering unfavorable reviews, only 18% had relationships with GSK.

The Senate committee blasted the role and structure of the FDA in then deciding the fate of Avandia, because those who make decisions about drug approvals are often in charge of the people who judge drug safety. It calls for a separate, independent pharmacovigilance unit to be established. The committee also wants a new FDA-ordered comparative study called TIDE stopped (comparing cardiovascular risks in both Avandia and other diabetes drugs).

However, the trial has been allowed to proceed, and there appear to be no references to these warnings from the safety officials in the consent form given to patients currently enrolling in TIDE, the Senate report claims.

* NEWS UPDATE:Glaxo Withheld Avandia Study, Ex-Regulator Said to Testify

July 12, 2010 – Dr. Rosemary Johann-Liang, a former manager in the FDA’s Drug Safety Unit, told lawyers suing GlaxoSmithKline that a 2001 study showing that Avandia posed a greater heart attack risk than rival medicines was withheld by the company. Glaxo also didn’t turn over an e-mail from researchers who concluded Avandia “strengthens the signals” of heart ailments, she testified in a pre-trial deposition last month.

Her FDA unit, which oversaw the safety of drugs already approved for sale in the U.S., recommended in 2006 that packaging labels for Avandia be upgraded to the highest level, with stronger warnings about the risk of heart failure listed in a black box. She testified that FDA officials, however, were upset with her recommendation, and waited 17 months before implementing it. In the meantime, they took away her power to make such recommendations, and even excluded her from attending safety review meetings. Dr. Johann-Liang, a pediatrician, left the FDA in June 2007 after six years with the agency.  Read the rest of the report.

If you are taking the prescription drug Avandia for Type-2 diabetes, contact your physician immediately to discuss a switch to a safer drug.

Read the whole Business Week report, or read GSK, FDA Under Fire In New Senate Report on Avandia.

* NEWS UPDATE: FDA to restrict Avandia, citing heart risk

September 24, 2010: In a highly unusual coordinated announcement, drug regulators in Europe and the United States said Thursday that Avandia, the controversial diabetes medicine, would no longer be widely available.

The drug’s sales will be suspended entirely in Europe, while patients in the United States will be allowed access to the medicine only if they and their doctors attest that they have tried every other diabetes medicine and that patients have been made aware of the drug’s substantial risks to the heart. Patients now taking Avandia may continue to do so.

Read the rest of this story from the New York Times.

News Update: Glaxo Hit With $3.4 Billion Charge

January 18, 2011:  GlaxoSmithKline has now taken $3.4 billion in charges to cover ongoing product-liability litigation and investigations into its handling of the controversial Avandia diabetes drug, which European regulators banned last fall because of its links to increased risk of heart attacks.

This charge brings the company’s total charges of litigation to over $6 billion. For some perspective, according to a report from Pharmalot, the most recent $3.4 billion charge could wipe out the company’s financial earnings from the last quarter. The charge greatly exceeds Avandia sales, which have been declining, not surprisingly, due to the ongoing publicity about the side effects.

New York Times, November 3, 2011:   GlaxoSmithKline Settles Investigation with Record $3 Billion Fine in Avandia Settlement