Delay In Trial Results Puts Companies In The Dock

Merck and Schering-Plough, the companies that make the drugs Vytorin and Zetia, have been found to deliberately delay the results of the trial of these drugs for the past two years.

The companies did not release the preliminary results of the trial, called Enhance, until January, almost two years after the trial was finished. When they were finally released, the trial’s results showed that the drugs, Vytorin and Zetia, did not work to reduce plaque in arteries. The results led a panel of cardiologists to recommend on Sunday that the drugs be used only as a last resort.

Senator Charles E. Grassley of Iowa, on Monday released the new information regarding the trial, in an e-mail addressed to the executives at Schering-Plough. Senator Grassley is a ranking Republican on the Senate Finance Committee. The committee has been investigating the delay in the release of the Enhance trial results.

Merck and Schering-Plough had been indulging in heavy promotion of the two drugs, ever since their release and even during the trial. The drugs are used to low cholesterol and are among the most widely prescribed medicines in the United States, with sales of $5 billion last year.

Shares of Merck and Schering plunged on Monday after the committee disclosed its findings. The committee suspects the companies of deliberately delaying the results to gain profits from the drugs, which had established well in the market.

Zetia lowers cholesterol by blocking its absorption in the intestine. Vytorin combines Zetia with Simvastatin, another cholesterol-lowering drug sold under the brand name Zocor.

The Enhance trial, done by the Dutch cardiologist Dr. Kastelein, consisted of images of the arteries of 720 patients taking either Vytorin which is the combination of Zetia and Zocor, or Zocor alone. Because Vytorin lowers cholesterol more than Zocor alone, the companies expected that the trial would show that patients who took Vytorin had less growth of plaque in their arteries than those who took Zocor. Arterial plaque is closely correlated with heart attack and strokes.

The trial had ended in April 2006, and its results were initially expected in late 2006 or early 2007. However, the companies did not declare the results delaying them for over two years, on some pretext or other.

The delay was infuriating Dr.Kastelein, and this was reflected in his messages to the company. “Is it correct that SP has decided not to present at AHA?” he said July 6 in an e-mail message to Dr. Rick Veltri, a vice president at the Schering-Plough Research Institute, referring to the American Heart Association conference in November.

“If this is the case, our collaboration is over,” he wrote, adding, “This starts smelling like extending the publication for no other [than] political reasons and I cannot live with that.”

Dr. Harlan M. Krumholz, a cardiologist at Yale, said Dr. Kastelein’s messages raised new concerns over the nearly two-year delay in the release of the Enhance results.

The delay was created against the wishes of the principal doctor involved. Thus, the recommendations of the company when released on Monday resulted in a plunge in the shares of Merck and Schering. Merck fell $6.56, or 15 percent, to $37.95. Schering, which is smaller and even more dependent on profits from Zetia and Vytorin, fell $5.06, or 26 percent, to $14.41.

Still, the drugs are widely used, with about three million prescriptions written each month in the United States alone. It remains to be seen, if the companies are ready to perform more large-scale and expensive tests to prove the worthiness of the drugs or not.