Avandia, a Deadly Case of Déjà vu all over again

nce again, a front page report in The New York Times (below) lays bare
unseemly facts about the pharmaceutical industry’s deadly norm and practice of concealing fatal risks of drugs that millions of patients consume as a result of aggressive marketing campaigns.

Once again, the FDA is shown to be complicit in turning a blind eye when a drug manufacturer, in this case, GlaxoSmithKline, concealed documented risks of heart attacks linked to its adjuctive diabetes drug, Avandia (rosiglitazone), putting of patients in harm’s way.

Gardiner Harris reports that a fierce debate that has been brewing for years within the FDA about “what to do about Avandia:” inasmuch as the preponderance of evidence shows patients taking the drug suffer cardiac harm.

nce again, a detailed Senate Finance Committee investigation reveals the
true magnitude of the potentially deadly cardiac risks involving Avandia, an aggressively marketed diabetes drug whose sales reached $3.2 billion in 2006, but whose deadly risks the manufacturer, GlaxoSmithKline, concealed
from patients and physicians for YEARS.” See Senate Finance Committee Press
Release packet: http://finance.senate.gov/press/Gpress/2010/prg022010b.pdf

he report, overseen by Senator Max Baucus, a Democrat, and Senator Charles E. Grassley, a Republican., examined 250,000 internal GSK documents, concluded that instead of issuing a warning—as is a drug manufacturer’s duty–

“G.S.K. 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.”

See Senate Finance Committee letter to FDA Commissioner (below).
The Committee packet posted on its website includes a comprehensive benefit-risk assessment report (2008. 75 pp.) by FDA safety officers, Dr. David Graham and Dr. Kate Gelperin.

hey report that the preponderance of evidence showed that “there was no evidence that rosiglitazone [Avandia] confers any unique health benefit over pioglitzone [Actos] while there was strong evidence that [Avandia] confers an increased risk of AMI [acute myocardial infarction] and heart failure compared to [Actos]. The evidence led these expert FDA safety officers to concluded that the drug “should be removed from the market” inasmuch as an estimated 500 heart attacks and 300 cases of heart failure would be averted EVERY MONTH, if patients took another diabetes drug.”

See Finance Committee packet Attachment B:
http://finance.senate.gov/press/Gpress/2010/prg022010a.pdf

Avandia’s cardiac risk was in evidence as early as November 2003, when GSK completed a study in which “diabetics given Avandia had far more heart problems than those given placebos.” European regulators ordered GSK to conduct a study to examine Avandia’s heart risks, but when the study showed harm (2004), GSK conducted a meta-analysis which it submitted to the FDA in 2005, and updated in 2006. The analysis showed that “Avandia increased the risks of serious heart problems by nearly a third.”

However, despite the totality of evidence, from company studies, adverse event reports filed with FDA’s Medwatch, and FDA safety evaluations corroborating Avandia’s deadly cardiac risks, the agency continued to drag its feet, “negotiating” with GSK, rather than pulling the drug off the market or, at the very least, issuing public warnings.

Even worse, in 2007, after the New England Journal of Medicine published a report warning of the cardiovascular risk for patients taking Avandia; and after warnings were issued in several countries–including Canada, the European Union, and Australia–that Avandia was CONTRAINDICATED in patients with acute coronary syndrome; FDA officials, in collusion and collaboration with GSK, approved an unethical and exploitative clinical trial—TIDE, which
is on-going. See:
http://clinicaltrials.gov/ct2/show/NCT00879970?term=nct00879970&rank=1

he trial does not meet the ethical principle of equipoise—requiring that so far as is known, benefit-risk of each comparator were equal. The accumulated evidence showed that Avandia posed higher risks than Actors. Furthermore, the FDA-approved trial allows the enrollment of very high risk patients with ischemic heart disease—for whom Avandia is contraindicated in several countries See: Attachment C:
http://finance.senate.gov/press/Gpress/2010/prg022010a.pdf
he Informed Consent form given to patients is deceptive by commingling the risks of Avandia with the comparator drug, Actos (pioglitzone), which does not pose the cardiac risk that Avandia does. See Finance Committee Attachment D: http://finance.senate.gov/press/Gpress/2010/prg022010a.pdf

Corporate tactics of intimidation are, once more, in evidence:

he Senate Finance Committee report states that “GSK executives intimidated independent physicians” who suggested in public that Avandia might have serious risks. It’s difficult to tell whether GSK took a leaf from Merck’s tactics of intimidation—such as, Merck’s physician “hit list” of doctors who publicly raised concerns about Vioxx cardiac risks—or whether intimidation of honest physicians is but “the norm and practice” within the
pharmaceutical industry.

FDA’s consistent failure to act in the public interest continues unabated under the Obama administration, much as it did under the Bush Administration. Avandia–and an untold number of other drugs that damage the heart–continue to be aggressively marketed, killing thousands of consumers: FDA officials continue to diddle.

by Vera Hassner Sharav: http://www.ahrp.org