June 5, 2009 / 9:17 PM / 11 years ago

Major study clears Glaxo's Avandia of heart risk

* Large study shows no overall raised cardiovascular risk

* Confirms higher risk of heart failure, fractures

* Glaxo to submit latest clinical data to FDA

* Unclear if study will revive Avandia sales

By Ben Hirschler

LONDON, June 5 (Reuters) - GlaxoSmithKline’s (GSK.L) controversial diabetes drug Avandia doesn’t increase overall heart risks, according to final results of a large clinical study sponsored by the world’s second largest drugmaker.

The so-called Record trial did, however, confirm that the medicine doubles the risk of heart failure — a chronic condition where the heart struggles to pump enough blood around the body — and also increases the danger of bone fractures.

Sales of Avandia, once Glaxo’s second biggest drug, plunged in 2007 after a pooled analysis of past clinical trials by Cleveland Clinic cardiologist Steven Nissen concluded patients on Avandia had a 43 percent higher risk of heart attacks.

Glaxo always contested those findings, arguing Avandia’s side-effect profile was no worse than that of other diabetes pills, citing interim results from the Record study to support its case.

But because the interim data covered only a limited number of adverse events, they were viewed with some scepticism.

Now, with full results in from the study that involved 4,447 patients over 5-1/2 years, Murray Stewart, vice president of clinical development, says Glaxo can deliver a conclusive rebuff to its critics.

“The final Record results show there is no difference in cardiovascular death or hospitalisation between Avandia and comparators,” he told Reuters in a telephone interview. “At the interim stage we couldn’t conclusively say that.”

The results of the study, which compared Avandia against the older drugs metformin and sulfonylurea, were presented at the American Diabetes Association annual meeting in New Orleans and published online by the Lancet medical journal.


Philip Home of Newcastle University, who led the trial, said it was good to have “robust evidence” that Avandia was no riskier than other diabetes drugs, particularly as the drug also proved superior in controlling blood sugar levels.

The higher risk of heart failure and fractures was a known effect common to the drug class, he said.

Home and colleagues said they could not rule some impact on heart attack incidence but any effect was marginal.

“Although our evidence is insufficient to rule out a small increased risk of myocardial infarction (heart attack) caused by rosiglitazone (Avandia) when compared with other glucose-lowering agents, rosiglitazone does not increase overall cardiovascular morbidity or mortality,” they wrote.

Glaxo’s Stewart said the full results of the study would now be assessed by the U.S. Food and Drug Administration, which tightened its warning on Avandia in November 2007.

“The FDA have seen the Record data and they’ve encouraged us to submit the data for consideration in the label, and we will do that,” he said.

Whether the latest data will be enough to revive Avandia’s commercial prospects remains to be seen. Glaxo has only limited time to try to ramp up sales again, since patents protecting the medicine expire in 2012 in the United States and 2013 in Europe.

Worldwide sales of Avandia totalled 805 million pounds ($1.29 billion) last year, representing around 3 percent of group sales.

In an accompanying Lancet commentary, Ravi Retnakaran and Bernard Zinman of Mount Sinai Hospital in Toronto and the University of Toronto suggested using half-maximum doses of Avandia, since half doses give better-than-half results, while limiting any side effects. (Editing by Dan Lalor) ($1 = 0.6232 pound)

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