Eleven dead in Alzeimer's drug trial

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Study of Alzheimer's drug raises questions of risk
Friday, March 17, 2006 Posted: 0619 GMT (1419 HKT)


CHICAGO, Illinois (Reuters) -- Eleven patients have died while taking Alzheimer's disease drug Aricept during a clinical trial, Japan's Eisai Co., which makes the medicine, said Thursday.

There were no deaths among patients who were taking a placebo, said Eisai, which markets Aricept with Pfizer Inc.

Aricept is already approved in most markets to treat mild to moderate Alzheimer's disease, but was being tested in patients with vascular dementia, the second most common form of dementia after Alzheimer's disease.

The news comes a day after Parexel International Corp. announced six people became seriously ill during a trial in Britain of an experimental drug for cancer and other inflammatory diseases. German firm TeGenero AG makes that drug. (Full story)

The negative headlines may lead to calls for greater scrutiny of clinical trials, some analysts said.

"You have the makings of a further pendulum swing to the conservative by regulatory agencies," said David Windley, an analyst at Jefferies.

The deaths were among 648 patients who received Aricept once daily for 24 weeks. That compared with no deaths in the 326 patients receiving placebos, Eisai said.

The difference in mortality between the groups was statistically significant, Eisai said, meaning it probably was not due to chance.

The Eisai trial is a Phase 3 study, the final period of testing before companies present proposals to regulators for approval.

An application to expand the use of Aricept to vascular dementia, caused by a stroke or diseased blood vessels, is pending in the United States, said Eisai spokeswoman Judee Shuler.

"We are still working with the FDA (Food and Drug Administration), discussing it," she said.

The company does not think the study changes the risk profile of the drug, she added. Pfizer officials did not have a comment.

Sam Gandy, chairman of medical and scientific advisory council of the Alzheimer's Association, said the findings "raise a red flag" but that it cannot negate 10 years of the drug's safety record on the market.

"It is very surprising, and it is of course of concern, but it is really outside the typical experience with the drug," said Gandy, who is also director of the neuroscience institute at Thomas Jefferson University in Philadelphia. "I would absolutely restrict its use to what it is approved for in Alzheimer's."

Aricept was considered innovative when approved in the mid- 1990s, improving upon a widely-used drug that caused liver toxicity, he said.

The trial was conducted in nine countries and involved only patients with vascular dementia, with no prior diagnosis of Alzheimer's disease. Most had a history of stroke or heart disease, and were therefore also taking medicines to treat their cardiovascular problems.

Eisai said it had not expected the absence of deaths in the placebo group, considering the age and sickness of patients in the study. By contrast, the company said there had been a combined 2 percent incidence of death among patients taking placebos in two prior vascular dementia trials.

The incidence of death in the Aricept group was similar to that in prior trials. But in these earlier studies, the difference between placebo deaths were not statistically significant.

Patients taking Aricept in the latest trial showed a statistically significant improvement in cognitive function, compared with those taking placebos. But the Aricept group showed no significant benefit on another primary measure of the trial, known as global function.

The drug is approved for vascular dementia in a half-dozen smaller markets, including South Korea and India.

Pfizer shares closed up 10 cents at $26.05 on the New York Stock Exchange trade. In Tokyo, Eisai closed down 0.4 percent on Thursday.

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