Evelyn Pringle June 5, 2007
On May 23, 2007, the Associated Press reported that more than 6 million people worldwide have taken Avandia (rosiglitazone), made by GlaxoSmithKline, to control blood sugar since it came on the market in 1999, and about 1 million patients in the US currently use the drug.
However, studies recently analyzed at the Cleveland Clinic shows Avandia users could have up to a 43% increased risk of heart attack and a 64% likelihood of an increase in heart- related disease.
On June 1, 2007, MedPage Today reported that doctors responding to an online survey "overwhelmingly rejected" the idea of prescribing Avandia for new patients with diabetes.
More than 200 participants completed the survey and 72% voted no to the question of whether they would start patients on rosiglitazone in view of the published report in the New England Journal of Medicine by cardiologist, by Dr Steven Nissen of the Cleveland Clinic, linking the drug to a 43% increase in the relative risk of myocardial infarction among those with diabetes.
Since the NEJM report was released online on May 21, 2007 Glaxo shares have declined 12% losing $19.7 billion of the firm's market value.
According to reporter Andrea Gerlin for Bloomberg News on June 1, 2007, Glaxo was the pharmaceutical industry's top advertiser last year, in promoting its diabetes and asthma treatments to patients and doctors.
Bloomberg reports that Glaxo spent $849 million on consumer advertising last year, citing information from Nielsen Monitor Plus, a unit of New York-based Nielsen Media Research.
In return, Avandia generated $3 billion in sales for Glaxo in 2006, or 7% of the company's total sales, Bloomberg says.
"Glaxo knew its Avandia diabetes pill posed a risk for heart and circulatory complications as early as 1999," the article states, "when the medicine won U.S. approval."
In an interview with Bloomberg on May 23, 2007, Dr Nissen said, "I just built this piece by piece until I had enough."
Until he found the Glaxo study that is. "Then I stumble upon the company's own meta analysis," he said, "deeply buried on their Web site, and it shows the same thing."
"It was a eureka moment for sure," he told Bloomberg.
Early last month Dr Nissen, chair of cardiovascular medicine at the Cleveland Clinic and immediate past president of the American College of Cardiology, was named one of the 100 Most Influential People by Time magazine.
In the magazine, best-selling author and cardiologist, Dr Mehmet Oz, described Dr Nissen as "a health crusader who devotes his time equally to developing medical protocols that can keep people well and exposing ones that don't."
In a May 3, 2007 interview with Heartwire, Dr Nissen said he can freely speak out on issues because "I have had fantastic support from the Cleveland Clinic to be able to say what I really think."
"I do take very clear positions on public issues," he acknowledged, "everything from stent safety to FDA reform."
But he's always had the support, he told Heartwire, "of an organization that said to me, 'Tell it the way you see it and we'll support you.'"
"Not everybody works at a place like that," he added.
However, it appears that the FDA is now on the attack against the man honored by Time Magazine last month. On May 30, 2007, Dr Nissen showed ABC News an e-mail sent to several health reporters by Douglas Arbesfeld, a senior communications consultant to the FDA and former spokesman for Johnson & Johnson.
In the e-mail, entitled "What are St. Steven's feet made of? Clay, perhaps?," Mr Arbesfeld forwarded a critical news article which included an anonymous blogger accusing Dr Nissen of playing favorites among drug companies.
Mr Arbesfeld included a comment on a blog posting, originally published in the Wall Street Journal, that accuses Dr Nissen of being critical of companies that do not support drug trials conducted at the Cleveland Clinic: "Wake up, pharmaceutical companies … if you don't hire the Cleveland Clinic for your big trials then you face the firing squad from Nissen and Company," it said.
Dr Nissen is more than a little upset. "I'm a pretty tough guy," he told ABC News, "but I'll tell you, having this kind of an e-mail that questions my motives, broadcast to the major journalists with whom I work and have established a reputation, is -- it's an outrage."
"Using taxpayer dollars," he pointed out, "a federal agency's press office, rather than responding to the scientific questions that I raised, attempting to smear me individually" is unacceptable.
FDA quickly tried to deny responsibility for the conduct of its spokesperson. In a statement to ABC News, the FDA said: "The content of the e-mail from an FDA consultant was his own words and does not represent an FDA position."
Dr Nissen told ABC News that he is even more infuriated that instead of addressing the Avandia study itself, a top FDA spokesman would distribute articles including the blog disparaging his reputation and that of the Cleveland Clinic.
"They're barking up the wrong tree," Dr Nissen told ABC. "While I did spend a sleepless night about this," he said, "I'm not backing down."
"What counts here is the health of our patients," he said. "And if they think they can intimidate me by doing this … they have another thing coming."
Glaxo's got plenty to worry about, but right about now using the FDA to defame reputable scientists is not a good idea. The FDA has its own Avandia troubles with both Houses of Congress demanding to know what the agency knew, when it knew it and why the FDA did not protect consumers from this new Vioxx-like disaster.
Last month, the FDA announced that it would form an advisory panel in response to a NEJM report. On May 25, 2007, a coalition of scientific, public health and consumer organizations issued a letter to the FDA asking for the exclusion of any scientists with financial ties to Glaxo
"In light of this study, and faltering public faith in the integrity of the FDA drug approval process," the letter said, "we write to urge you to ensure that the composition of any advisory committee that is being convened to review the safety of Avandia be free of any conflict of interest."
"At the minimum," the Group wrote, "no member of this committee should have had any financial ties to GlaxoSmithKline, Avandia's maker, for the past 36 months."
Glaxo will probably be stuck in damage control mode for quite awhile. On May 21, 2007, the day the NEJM report was made pubic, Morgan Stanley analysts led by Andrew Baum warned in a note that Avandia is facing new competition and reports of a heart risk may lower sales by as much as 50%. Glaxo's "robust defense of Avandia safety and their conduct comes with a high risk if evidence of poor disclosure subsequently emerges," Mr Baum wrote.