The Food and Drug Administration said that it is considering, but has not yet determined, whether data from the ENHANCE study of Vytorin warrants any regulatory action.
The agency posted an “early communication” and a MedWatch safety report on its Web site alerting the public and health care practitioners that it is aware of the data but that it has not yet fully examined what appear to be equivocal results.
In a press briefing, Dr. John Jenkins, director of the FDA's Office of New Drugs, said the agency hopes to determine why the ENHANCE (Effect of Combination Ezetimibe and High-Dose Simvastatin vs. Simvastatin Alone on the Atherosclerotic Process in Patients with Heterozygous Familial Hypercholesterolemia) trial results were equivocal, with the combination not affecting plaque size in carotid arteries.
Agency officials who participated in the briefing said they were scratching their heads over the results, given that both ezetimibe and simvastatin have been shown to lower LDL cholesterol levels in ENHANCE and in other studies. LDL is a validated surrogate end point, they said.
FDA reviewers will evaluate the data with an eye on potential safety issues, Dr. Jenkins said. “We don't see any reason to change the label or the approved indications based on this study,” he said.
He said it may take several months for the agency to receive the data from Merck & Co. and Schering-Plough Pharmaceuticals, the companies that conducted the ENHANCE study, and up to 6 months after that to complete the review.
A press release revealing the equivocal results issued by Merck and Schering-Plough set off a firestorm of criticism. The House Energy and Commerce Committee and the Senate Finance Committee are investigating the timing of the data release and myriad other issues around Vytorin. It also prompted a torrent of class action suits alleging marketing fraud by the two drug makers.
The agency said physicians should not stop prescribing Vytorin or Zetia (ezetimibe), but should, in conjunction with patients, “carefully consider the available data and current labeling for Zetia and Vytorin as they make individual treatment decisions.”
Dr. Jenkins pointed out that neither of these products has any data on reduction of heart attack or stroke as of yet. Cardiovascular events will be measured in the companies' ongoing Improved Reduction of Outcomes: Vytorin Efficacy International Trial (IMPROVE-IT), which will be completed in 2011.
“If a physician wants the certainty of using a product that has outcomes data, [there are] a large number of those products available,” he said.
Merck and Schering-Plough “acted with integrity and good faith in connection with the trial,” said Thomas Koestler, Ph.D., president of the Schering-Plough Research Institute. “We stand behind Vytorin and Zetia and stand behind our science,” said Peter S. Kim, Ph.D., Merck Research Laboratories president.