Alzheimer's drug fails panel review.

Alzheimer's drug fails panel review

Despite some favorable testimony, an advisory panel has decided against recommending that the FDA approve the marketing of an experimental Alzheimer's drug. In announcing its conclusion last week, the panel cited a lack of convincing scientific evidence demonstrating the efficacy and safety of the drug, known as tetrahydroaminoacridine (THA). The decision means the compound's manufacturer, Warner-Lambert Co., must gather additional data before it can win FDA approval of the controversial drug to treat a disease for which no drug therapy now exists.

This isn't the first time questions about THA have surfaced. Psychiatrist William K. Summers of Arcadia, Calif., launched the THA saga in November 1986 with a report of dramatic improvement in 12 Alzheimer's patients who had taken the drug for about a year. Although researchers hailed THA as a major treatment breakthrough at the time, a subsequent FDA probe revealed serious flaws in the study (SN: 2/2/91, p.70).

Now, two new studies -- one conducted by U.S. researchers and the other by British scientists -- add mixed results to the growing file on THA.

Officials at Warner-Lambert, which helped sponsor the trials, presented unpublished results from those studies at last week's advisory panel meeting in Rockville, Md. Although measures of cognitive ability showed that THA provided some clinical benefit in both trials, another type of cognitive test revealed no improvements from THA compared with placebo. After deliberating for nearly 14 hours, the FDA panel decided the slight improvements seen on some tests did not outweigh the drug's small but potentially serious threat of liver damage (SN: 11/7/87, p.292).

In one of the studies, led by Kenneth L. Davis at the Mount Sinai School of Medicine in New York City, investigators at 16 U.S. clinical centers randomly assigned 112 Alzheimer's patients to placebo and 103 to THA. Neither the researchers nor the volunteers knew who got the active drug. After six weeks, the team found that people on THA, compared with placebo recipients, scored an average of three points higher on the Alzheimer's Disease Assessment Scale, a test measuring memory, language and other thinking abilities that progressively fail among victims of the disease. While this difference was small, the researchers call it significant.

However, THA's performance faltered on the Clinical Global Impression of Change, a test commonly used to gauge the general state of psychiatric patients, including thinking skills. Scrutiny of those scores revealed no difference between THA treatment and placebo.

In the British study, a 29-week trial involving 92 people with Alzheimer's, researchers led by Raymond Levy of the Institute of Psychiatry in London randomly assigned half the participants to a placebo and the remainder to THA plus lecithin, a substance thought to boost THA's efficacy. Halfway through the trial, they switched the two groups so that people on the placebo got the active drug and vice versa. Using a test called the Mini-Mental State Examination, the investigators discovered that 44 percent of the volunteers improved their scores by three or more points after treatment. Only 11 percent showed a similar rise in scores after receiving the placebo.

Despite the varying results measured on different cognitive tests, some clinicians say their own experience has convinced them of THA's promise. Nancy L. Earl, a neurologist at Duke University in Durham, N.C., told the FDA panel that some of her patients with Alzheimer's show enhanced cognitive abilities with THA treatment. "I know that I saw significant improvement in some patients at my site," she said.

But such testimony remains purely anecdotal, and the FDA remains unswayed. Officials at the agency want to see more hard data proving THA's potency and safety before granting Warner-Lambert the go-ahead to market this treatment to an estimated 4 million people in the United States who suffer from Alzheimer's disease.