Vytorin misses study goal

July 21, 2008 8:43:07 PM PDT
In the latest disappointment over 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. Its makers' shares plunged about 15 percent.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 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 elderly people, involves blockage and stiffening of the aortic valve, which sends oxygen-rich blood through the aorta and on throughout 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 sites in Europe were hoping the study, called SEAS, would show Vytorin offers a nonsurgical way to treat aortic stenosis.

That wasn't the case, although Vytorin did cut cholesterol levels about 60 percent.

The findings overshadowed second-quarter results for the two companies, which held up the results from Monday morning until the end of the day to allow researchers involved with SEAS to discuss the findings with reporters and analysts.

Vytorin, which combines Merck's Zocor - now available as a cheap generic - with Schering-Plough's Zetia, didn't 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, Sir Richard Peto, an Oxford University statistician and cancer expert who analyzed the data, told The Associated Press in an interview.

The study of 1,873 patients aged 45 to 85, just ended in March, did find that secondary benefit, but it's already known that some cholesterol-lowering drugs reduce 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 percent more new cancer cases and cancer deaths in patients who received Vytorin, compared with those who took a placebo. Peto, co-director of Oxford's clinical trial service unit, then rushed to crunch data from the new study with patient data from two much-larger, ongoing Vytorin studies.

Peto and other researchers, speaking on a hastily organized, trans-Atlantic teleconference with reporters, said combining 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-percent increase in risk," Peto said.

Dr. Harlan Krumholz, a Yale University cardiologist, said he doubts Vytorin causes cancer.

"If I'm a patient considering taking it, it still bothers me," he said, adding that until the other Vytorin studies are finished in a few years, it will remain unclear whether and how the drug benefits patients beyond what Zocor and other statins do.

Earlier this year, a long-delayed study called ENHANCE found pricey Vytorin was no better at reducing plaque buildup than generic Zocor, which costs one-third as much.

Meanwhile, Merck posted a 5 percent rise in second-quarter profit, weathering drops in sales of Vytorin, Zetia and asthma drug Singulair with stringent cost controls.

Net income rose to $1.77 billion, or 82 cents per share, from $1.68 billion, or 77 cents per share, during the prior-year period.

That's despite sales edging down 1 percent, to $6.05 billion.

Excluding restructuring charges, Merck said it earned 86 cents per share, 3 cents more than analysts expected.

Schering-Plough Corp.'s second-quarter profit also beat Wall Street expectations by 3 cents, even though net income dropped 23 percent on one-time charges.

It earned $398 million, or 24 cents per share, down from $517 million, or 34 cents per share, a year earlier. Excluding accounting adjustments and charges for ending a program with Merck to gain approval of a combination allergy drug already rejected by U.S. regulators, Schering earned 45 cents per share.

Sales rose 55 percent to $4.92 billion, mainly due to last fall's Organon BioSciences purchase; including Schering-Plough's share from the cholesterol joint venture, they totaled $5.5 billion.

Two congressional committees have been probing whether the companies deliberately delayed releasing the ENHANCE data to prop up sales of Vytorin, which the companies denied. Sen. Chuck Grassley, the top Republican on the Senate Finance Committee, urged the companies late Monday to respond fully to inquiries he's made about Vytorin, saying they ought to be more responsive "given the public safety and public expenditures involved with Vytorin."

Prominent cardiologists have urged doctors to go back to older, well-proven treatments for high cholesterol.

Many apparently did. Last week, Schering-Plough reported the number of U.S. prescriptions filled for Vytorin and Zetia had both fallen by just over 25 percent from January to June, when total cholesterol drug sales were down about 5 percent.

Shares of Kenilworth, N.J.-based Schering-Plough finished Monday down $2.49, or 11.6 percent, at $18.95, then dropped another 68 cents in after-hours trading. Shares of Whitehouse Station, N.J.-based Merck fell $2.35, or 6.2 percent, to $35.33, then dove another $2.49, or 7 percent, after hours.