|Trial results may have major affect on Vytorin sales. Source: Alex Constantine|
Despite catchy TV commercials claiming Vytorin's positives of reducing cholesterol levels in patients predisposed to high cholesterol levels, a just-released study found Vytorin is no more effective in treating patients who were genetically predisposed to having dangerously high levels of cholesterol than Merck's drug Zocor (Vytorin contains Zocor) because it did not slow the growth of artery blockages. Merck/Schering-Plough Pharmaceuticals reported the results of the ENHANCE trial.
Vytorin contains Zocor, which recently lost patent protection and is now available generically as simvastatin, and a newer drug called Zetia. About 60 percent of patients who take Zetia take it with Zocor as Vytorin, according to USA Today.
ENHANCE — officially called Effect of Combination Ezetimibe and High-Dose Simvastatin vs. Simvastatin Alone on the Atherosclerotic Process in Patients with Heterozygous Familial Hypercholesterolemia — examined 720 patients with very high levels of cholesterol from an inherited heart disease (heterozygous familial hypercholesterolemia), a condition that affects about 0.2 percent of the population. The primary endpoint was the mean change in the intima-media thickness (IMT) measured at three sites in the carotid arteries between patients treated with ezetimibe/simvastatin 10/80 mg versus patients treated with simvastatin 80 mg alone over a two-year period.
The companies reported that there was no statistically significant difference between treatment groups on the primary endpoint. At baseline, the mean carotid IMT measurement for ezetimibe/simvastatin was 0.68 mm and for simvastatin 80 mg was 0.69 mm. The change from baseline in the mean carotid IMT was 0.0111 mm for the ezetimibe/simvastatin 10/80 mg group versus 0.0058 mm for the simvastatin 80 mg group. There was also no statistically significant difference between the treatment groups for each of the components of the primary endpoint, including the common carotid artery, according to the Whitehouse Station, N.J.-based Merck and the Kenilworth, N.J.-based Schering-Plough. The companies also reported that the safety profiles of ezetimibe/simvastatin and simvastatin alone were similar and generally consistent with their product labels.
Specifically, the incidence rates of cardiovascular clinical events in ENHANCE for the ezetimibe/simvastatin and simvastatin groups, respectively, were as follows: cardiovascular death 2 out of 357 vs. 1 out of 363; non-fatal myocardial infarction 3 out of 357 vs. 2 out of 363; non-fatal stroke 1 out of 357 vs. 1 out of 363; and revascularization 6 out of 357 vs. 5 out of 363. There were no non-cardiovascular deaths or incidents of resuscitated cardiac arrests in the ENHANCE trial.
Based on the results, Steven Nissen, MD, the Cleveland Clinic's chief of cardiology, who called the findings "stunning," told USA Today that Vytorin is "certainly not an alternative to high doses of statins, which we know work."
Roger Blumenthal, MD, of the Johns Hopkins Ciccarone Center for the Prevention of Heart Disease and the American College of Cardiology prevention committee, told USA Today, that "Zetia and Vytorin should not be used as first-line drugs. They're most useful for patients who aren't getting all the help they need from statins and for those who can't tolerate statins' side effects, including liver problems."
Vytorin has emerged as a huge moneymaker for Merck with about $5 billion in annual sales globally. According to NBC News, Zetia and Vytorin consume 20 percent of the cholesterol-lowering drug market at $3 to $4 a pill in the United States. Comparatively, the generic simvastatin costs about $1 per pill. According the New York Times, approximately 800,000 prescriptions are written for Vytorin globally per year.
As CVB News reported, the accusation that Merck and Schering-Plough was withholding the results caused Reps. John Dingell, D-Mich., and Bart Stupak, D-Mich., who chairs an Energy and Commerce subcommittee on oversight and investigations, to ask the companies to explain their delay in releasing data from the ENHANCE trial, completed in April 2006. Dingell and Stupak Monday said they are continuing the investigation that they started on Dec. 11.
Merck/Schering-Plough Pharmaceuticals said they are currently conducting three larger outcomes trials with ezetimibe/simvastatin, involving more than 20,000 high-risk patients, including