Merck & Co should not be allowed to claim that its cholesterol-lowering drug Vytorin reduces the risk of heart attacks and strokes in patients with coronary heart disease, an advisory committee to the U.S. Food and Drug Administration concluded on Monday.
The panel evaluated data from an 18,000-patient trial known as Improve-It whose results showed that the combination treatment known as Vytorin, comprising Zetia and an older cholesterol-lowering drug, simvastatin, reduced the rates of heart attack, stroke and death compared with simvastatin alone.
But the panelists voted 10-5 against allowing Merck to make the claim, saying they were not convinced the benefit was clinically meaningful, especially since some patient data was missing.
“The benefit here is small,” said Dr. Milton Packer, distinguished scholar in cardiovascular science at Baylor University Medical Center. “It is not robust. You blink and you miss it, and you wonder if you care or don’t care.”
The FDA is not obliged to follow the advice of its advisory panels but typically does so.
“Today's discussion is one step in the regulatory process,” Dr. Daniel Bloomfield, vice president of cardiovascular disease at Merck Research Laboratories, said in a statement. He said the company would continue to work with the FDA “so that they can complete the review” of its request for new indications for Vytorin and Zetia.
“We believe Improve-It showed that ezetimibe in combination with a statin offers a significant benefit to high-risk patients with coronary heart disease,” he said. Zetia is Merck's brand name for ezetimibe.
In the Improve-It study, Vytorin reduced the risk of heart attacks, strokes and other heart problems by 6.4 percent compared with patients who took simvastatin alone, meeting the main goal of the trial.
Simvastatin is sold by Merck under the brand name Zocor.
Some panelists said that result should have been enough to support approval.
Dr. William Hiatt, a professor at the University of Colorado School of Medicine, said the FDA's role is to determine whether the results of a trial are statistically significant. Other organizations, he said, such as payors, typically decide whether they are clinically meaningful.
Vytorin and Zetia are both currently approved to reduce “bad” LDL cholesterol. Vytorin has long been used in the hope it reduces cardiovascular events, but Merck has not been allowed make those claims in its marketing material because the FDA has not approved it for that use.
By Toni Clarke Reuters