In European study, Vytorin fails to meet expectations
In the latest disappointment for cholesterol pill Vytorin, a major European study in patients with heart valve disease found the drug didn’t prevent worsening of the disease or lower the need for valve surgery, sending its makers’ stock plunging.
Results of a preliminary analysis of the just-completed study showed Vytorin, marketed jointly by Merck & Co. and Schering-Plough Corp., was no better than a placebo at lowering the risk of major cardiovascular events -- including heart attack, stroke, heart surgery and death -- in patients with aortic stenosis.
The sometimes deadly condition, which is becoming increasingly common in the elderly, involves partial blockage and stiffening of the aortic valve, which sends oxygen-rich blood from the heart to the rest of the body. More than 5 million Americans have the disease to some extent, and it’s the No. 2 cause of heart surgery.
Researchers at 173 hospitals and other sites in Europe were hoping the study, called SEAS, would show that Vytorin offered a nonsurgical way to treat the condition by reducing bad cholesterol levels and plaque buildup.
That wasn’t the case, although Vytorin did cut cholesterol levels about 60%.
But Vytorin, which combines Merck’s Zocor -- now available as an inexpensive generic -- with Schering-Plough’s Zetia, didn’t do anything to protect patients’ heart valves and raised fears, apparently unfounded, that it increased risk of cancer.
“You don’t help that [valve] disease, but you do help the patients” by protecting other heart blood vessels and reducing heart attacks and the need for bypass surgery or artery-clearing angioplasty, said Richard Peto, an Oxford University statistician and cancer expert who analyzed the data.
The 1,873-patient study, which ended in March, did find that secondary benefit, but it’s already well-documented that some cholesterol-lowering drugs reduce the risk of heart attack and stroke.
The cholesterol-lowering and reduced heart complications are consistent with what’s been shown with Zocor alone, said Cleveland Clinic cardiologist Dr. Steven Nissen, who recommends that Vytorin and Zetia not be used as first-line drugs.
“We are left with just as many questions about the efficacy of Vytorin [as before], and we have new questions about the safety,” he said, referring to the excess cancer cases and deaths in Vytorin users.
When data analysis began, the researchers were startled to see about 50% more new cancer cases and cancer deaths in patients who received Vytorin, compared with those who took a placebo. Peto, who is co-director of Oxford’s clinical trial service unit, then rushed to combine data from the new study with patient data from two much-larger, ongoing Vytorin studies.
Peto and other researchers said the summarized data from all three trials showed there was no elevated risk of cancer. In addition, they noted that if Vytorin were somehow triggering cancer, new cases would first become more common after several years and would be concentrated on one type of cancer, rather than many. Neither was the case.
“This absolutely excludes the idea of a 50% increase in risk,” Peto said of the multistudy analysis.
Shares of Kenilworth, N.J.-based Schering-Plough finished Monday down $2.49, or 11.6%, to $18.95, while shares of Whitehouse Station, N.J.-based Merck were down $2.35, or 6.2%, to $35.33.
