New England Journal of Medicine Prints Report Critical of GlaxoSmithKline Drug (Updated)

The Boston Globe reported today that a new study released early by the New England Journal of Medicine on its website questions the safety of one of the largest-selling diabetes medications in the country, Avandia.

Avandia, the world’s top-selling oral diabetes drug, significantly increases the risk of heart attacks, a prominent cardiologist said in an article that the New England Journal of Medicine deemed important enough to post on its website yesterday, weeks before the scheduled print publication date.

Dr. Steven E. Nissen, a cardiologist at the Cleveland Clinic and the article’s lead author, pored through summaries of dozens of studies and found a 43 percent higher risk of diabetics suffering a heart attack if they took Avandia compared with other drugs or sugar pills. Nissen was unable to determine whether the risk is affected by how long Avandia is used or how much is taken.

***

“The leading cause of death in diabetes is heart disease. It causes between 65 to 80 percent of all diabetes mortality,” Nissen said in an interview. “When a diabetes drug, which is intended to reduce the risk of diabetes complications, actually increases it, it has profound public health consequences.”

In an accompanying editorial published by the New England Journal of Medicine, Bruce Psaty and Curt Furberg, doctors who are critics of the FDA’s drug-approval process, said there is little reason for doctors to prescribe Avandia….

(emphasis added)

The drug is produced by GlaxoSmithKline, a major player in Big Pharma, and is worth over $$$3BIL$$$/year in sales worldwide. GSK immediately attacked the report, claiming it’s “flawed”.

That’s not particularly surprising, nor is it surprising that after the Vioxx debacle, the release of the report triggered a nosedive of GSK’s stock.

Since the Food and Drug Administration approved Avandia in 1999 doctors have written tens of millions of prescriptions for the drug. The Journal released the paper in advance of its June 14 print publication date partly because of its public health impact, according to executive editor Dr. Gregory Curfman.

Investors and others, including members of Congress, yesterday reacted strongly to the article.

GlaxoSmithKline shares closed at $53.18, down 7.85 percent, in heavy trading.

(emphasis added)

The big question here is, “Where was the FDA?”

In the 6 years of the Bush Administration, the FDA’s budget has been slashed every single year. During the food scares in February, Newsday reported that one of the consequences of that budget-cutting has been drastically-reduced inspections.

The federal agency that’s been front and center in warning the public about tainted spinach and contaminated peanut butter is conducting just half the food safety inspections it did three years ago.

The cuts by the Food and Drug Administration come despite a barrage of high-profile food recalls.

Between 2003 and 2006, FDA food safety inspections dropped 47 percent, according to a database analysis of federal records by The Associated Press.

That’s not all that’s dropping at the FDA in terms of food safety. The analysis also shows:

  • 12 percent fewer FDA employees in field offices who concentrate on food issues.
  • Safety tests for U.S.-produced food have dropped nearly 75 percent, from 9,748 in 2003 to 2,455 last year, according to the agency’s own statistics.

Those statistics certainly suggest the likelihood that the FDA’s used-to-be rigorous drug testing procedures have been cut short due to lack of funds, but that’s not the only problem. Last year, a retired associate commissioner at the FDA, William Hubbard, complained in a WaPo op-ed that the FDA wasn’t to blame for poorly-tested drugs making it to market.

When the public clamored a decade ago for faster access to new drugs, the FDA developed procedures to get lifesaving drugs on the market in less time — for instance, by allowing much data about a drug’s safety to be gathered after the drug was approved. But there was a trade-off: FDA scientists would accept greater risk that safety problems could slip through, while drug companies would continue to study the drugs for such problems (and Congress would give the FDA authority to compel such study if needed).

FDA scientists have done as they promised — new drugs have been sped to market, and the FDA leads the world in approval times. But the companies often fail to do the needed safety studies, and Congress has taken no steps to allow the agency to compel them. FDA scientists also recognized that rapid drug approvals can miss important safety indicators and requested funding to create state-of-the-art systems to monitor drug safety. The new dollars that the White House proposed and Congress provided for this come to a nice round number: zero.

Hubbard insisted that there had been “a pattern of neglect [of the FDA] by officials of both parties in the White House and Congress” and he was right about that. He was wrong, however, when he placed the blame for rushed judgments on “the public”. The public wasn’t “clamoring…for faster access to new drugs”. That noise was all coming from Big Pharma lobbyists hired to get the Republican Congress to shorten the time between development of a drug and the profits it could rake in.

He also managed to leave out the fox Bush put in charge of the FDA henhouse in November of ’02.

Mark McClellan was FDA Commissioner during the formative years of Bush’s transformation of govt watchdog agencies into subsidiaries of the industries those agencies were supposed to regulate. McClellan’s primary expertise was not medicine but economics – conservative economics. He came in as a budget-cutter and service-slasher direct from a stint at the ultra-right-wing American Enterprise Institute where it is an article of faith that all govt interference with business is BAD.

He created in the FDA a culture of slash-and-burn budget-cutting intended to bring it in line with the AEI’s single-minded vision of a crippled govt unable to check corporate profits by stopping unsafe or unhealthy food and drugs from being big money-makers for Agri-business and Big Pharma. The two caretaker Commissioners who followed him – Lester Crawford and the present Commish, Andrew von Eschenbach – have done nothing to reverse that trend. Of course, if they tried, Bush would most likely fire them.

The consequences – e.coli outbreaks and inadequately-tested drugs – haven’t been pretty but they haven’t yet gotten ugly.

That comes next.

Full Disclosure: I was recently diagnosed with Type 2 diabetes. I do not take Avandia.

Update: The New York Times is reporting that GSK’s rush to market with Avandia and the consequent publication of the NEJM article warning of serious side effects may stall or even derail the clinical study meant to test the drug’s safety: patients enrolled in the study are pulling out.

Dr. Ronald L. Krall, the medical director for GlaxoSmithKline, said in a telephone interview yesterday that some of the 4,450 patients enrolled in the drug trial, called Record, have dropped out this week because of safety concerns about Avandia.

Dr. Krall said he did not yet know how many patients have withdrawn, but said Glaxo was now worried about whether it could complete the drug trial, which has been scheduled to run through next year. The company has been counting on a successful outcome from the study to dispel widespread concerns that Avandia carries a higher risk of heart attacks than other diabetes drugs.

The in-the-corporate-tank FDA is downplaying its own findings, its spokeswoman virtually promising GSK that FDA will concentrate on the up-side.

“Dr. Nissen’s meta-analysis and the F.D.A.’s meta-analysis both arrived at a similar figure of 40 percent” the F.D.A. spokeswoman, Julie Zawisza, wrote in an e-mail message. “But this alone, is not conclusive of anything. What it does mean is that we need to try to reconcile the meta-analysis finding with clinical trial data that DO NOT show this increased risk.”

IOW, find a reason to approve the drug no matter what. If they know nothing else – and they don’t – those Bushies certainly know which side of the bread the butter is on. And who put it there.

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2 Responses

  1. The study authored by Stephen Nissen and Kathy Wolski has been freely and continuously available since Monday morning at nejm.org. The study can be found at:

    http://content.nejm.org/cgi/content/full/NEJMoa072761

    The study is still featured on the homepage of nejm.org. At 5:30 pm on Tuesday May 22, it was the first original article listed on the NEJM homepage, right below the Clinical Decisions feature in the center column of the homepage. The study will appear in the print journal dated June 14, 2007.

    At the top of the homepage, NEJM is displaying a link to another early release article titled “Burch Colposuspension versus Fascial Sling to Reduce Urinary Stress Incontinence.” This link replaced the link to the Rosiglitazone study.

  2. I apologize for the mistake. The post has been edited to correct it.

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