Issue Date: April 7, 2008
Trial Results Roil Drug Companies
MERCK & CO. and Schering-Plough are facing harsh criticism from lawmakers who say the companies held back negative clinical trial data so that they could continue to profit from sales of their cholesterol-lowering drugs Vytorin and Zetia.
Nearly two years after the end of a clinical trial called Enhance, researchers reported that Vytorin—a combination of simvastatin and Zetia (ezetimibe)—was no better than simvastatin alone in preventing the buildup of arterial plaque. The complete results were presented on March 30 at an American College of Cardiology (ACC) meeting and are published in the New England Journal of Medicine (2008, 358, 1431).
At the ACC meeting, a panel of five medical experts recommended that doctors prescribe statin-based drugs first rather than Vytorin or Zetia. Statins limit cholesterol synthesis in the body, whereas ezetimibe prevents the absorption of dietary cholesterol. Both lower levels of LDL (bad) cholesterol, but only statins have been shown to reduce heart attacks and deaths; studies are under way to show whether Zetia can do the same.
A day after the results were presented, Sen. Charles E. Grassley (R-Iowa) chastised the companies in writing for not giving doctors the facts earlier so that they could make informed decisions. The lack of information, he added, imposed financial burdens on patients and the government, which had spent hundreds of millions of dollars on Vytorin in the two years since the end of the trial.
The Senate Finance Committee, on which Grassley serves, as well as the House Energy & Commerce Committee and the New York State attorney general's office have been investigating whether the companies delayed publication for marketing purposes. A Schering-Plough spokeswoman says, "We are cooperating fully, and we stand behind our products as we have done nothing wrong."
Among other things Grassley questioned money that the companies' joint venture budgeted to promote Vytorin. "I remain troubled that Merck/Schering-Plough failed to report any results from the Enhance trial until January 2008 while trying over the past year or two to get doctors to switch their patients to Vytorin from other, less expensive statin drugs," he wrote. The joint venture's combined sales of Vytorin and Zetia were $5.2 billion in 2007 and accounted for 15% of the U.S. cholesterol-lowering drug market.
Grassley published disparaging e-mail excerpts from John Kastelein, lead investigator for the Enhance trial, to the joint venture. "This starts smelling like extending the publication for no other [than] political reasons," Kastelein wrote. To show the comments in context, Schering-Plough has released what it says is the full text of e-mails "concerning an issue that Merck/Schering-Plough and, we believe, Dr. Kastelein considered long resolved," the Schering-Plough spokeswoman says. (Go to www.cen-online.org for links to the e-mails and Grassley's letter.)
The companies assert that the study took longer than anticipated to complete due to unexpected challenges in analyzing the data. But once these issues were addressed, they disclosed initial results just two weeks after the study was unblinded in late 2007, the spokeswoman says, and then assisted Kastelein in promptly publishing and presenting the full results.
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