UPDATE 2-Glaxo's Avandia fails to slow plaque progression

(Adds researcher and company comments, study details, background)

By Bill Berkrot and Ransdell Pierson

NEW ORLEANS, Nov 12 (Reuters) - GlaxoSmithKline Plc's (GSK.L) diabetes medicine Avandia failed to significantly reduce progression of plaque buildup in coronary arteries in a clinical trial presented at a major heart meeting on Wednesday.

A positive outcome would have been welcome news for Glaxo as Avandia has been under a cloud since an analysis of past clinical studies appeared to find increased risk of heart attack not seen with similar diabetes medicines.

Sales of the drug fell 23 percent in the third quarter to $314 million and Glaxo was forced to defend the drug again last month amid charges from a public advocacy group that Avandia had caused more than a dozen cases of liver failure.

The new clinical trial of 672 patients with type 2 diabetes and heart disease compared Avandia's impact on atherosclerosis -- or buildup of fatty plaque in the arteries -- with that of a much older, generically available diabetes medicine called glipizide.

After 18 months of treatment, those who took Avandia, known chemically as rosiglitazone, had an 0.21 percent reduction in plaque at the observed artery, while glipizide patients experienced an 0.43 percent increase in plaque. Although Avandia results appeared to be numerically better, they did not achieve statistical significance, researchers said, meaning the results could have been by chance.

"This study supports but does not prove the hypothesis that rosiglitazone has greater anti-atherosclerotic effect than glipizide in patients with type 2 diabetes," said Dr. Richard Nesto, lead investigator of the study, who presented the data at the American Heart Association scientific meeting in New Orleans.

An earlier study that tested Avandia rival Actos from Takeda Pharmaceutical Co (4502.T) against a similar drug to glipizide did find a statistically significant reduction in plaque progression, researchers noted.

Glaxo issued a statement saying it was encouraged by findings from the study. But the lack of conclusive proof that Avandia stalls atherosclerosis progression and the obvious comparison to the Actos data will likely do little to remove the cloud hanging over the medicine.

Avandia was statistically significantly better than glipizide in a secondary goal of the study that measured total volume of blood vessel blockage after 18 months of treatment.

And the Glaxo drug did have significantly fewer low blood sugar incidents -- just 8 percent compared with 28 percent of patients taking the older drug.

Avandia belongs to a relatively new class of diabetes medicines called thiazolidinediones, or TZDs, that work by making the body's cells more sensitive to insulin. Glipizide, which has been in use for more than 40 years, is from the sulfonylurea class, which makes the pancreas secrete more insulin.

Diabetics are at increased risk for a multitude of serious health problems, including atherosclerosis, heart attacks and stokes.

Patients in the study were an average age of 61 and undergoing coronary procedures such as angiography or plaque-clearing angioplasty.

Using intravascular ultrasound (IVUS), researchers measured plaque in a 40 millimeter segment of an artery not involved in the procedures and measured the same artery 18 months later to determine the results of the study.

Noting the "substantial controversy regarding the use of rosiglitazone," Dr. Beatriz Rodriguez of the Pacific Health Research Institute in Honolulu said, "the findings of this study need to be interpreted with caution." (Editing by Matthew Lewis)