Still No Relief from Alzheimer's

By Anastasia Toufexis

Woodrow Wirsig shudders to recall his wife Jane's gradual 10-year decline from Alzheimer's disease. At the low point, she was mute and immobile. But then in 1987, as part of an experimental program, she was put on the drug tacrine. "Within weeks," says Wirsig, of Palm City, Fla., "she could walk and talk and recognize me from 90 ft." Such stories have given tacrine a reputation as a Lazarus drug, the one medication that could recall to life loved ones who are losing control of their minds and bodies.

But access to the experimental drug is strictly limited, and for years desperate families have been pressing the Food and Drug Administration to make it widely available. Last week an FDA advisory panel issued a strong rebuff. After reviewing all the clinical studies, the panel agreed 8-0 that tacrine "did not show a clinically meaningful benefit." Moreover, the danger of its causing liver damage is significant, the group said.

The tacrine controversy underscores one of the most vexing of medical issues: should the regulatory process be eased for drugs aimed at deadly diseases that do not respond to any other treatment? Vigorous lobbying by AIDS activists has led the FDA to expedite release of two drugs that appear to alleviate symptoms of that fatal infection. Inspired by that example, families of Alzheimer's patients have been demanding similar treatment.

The clamor for tacrine, also known as THA (for tetrahydroaminoacridine), started in 1986 when the New England Journal of Medicine reported a study in which 16 of 17 patients given the drug had shown marked improvement. The results seemed miraculous, but they made scientific sense: the brains of Alzheimer's victims have abnormally low levels of acetylcholine, a chemical that carries impulses from one nerve to another. Tacrine inhibits production of an enzyme that breaks down the chemical messenger, thus presumably making more acetylcholine available.

According to Warner-Lambert, which has U.S. marketing rights to the drug, a National Institute on Aging study of 200 patients at 16 hospitals found that among those receiving tacrine, more than 40% showed some improvement in performing mental or physical tasks. Based on this and other data, the company asked the FDA last March for approval to market tacrine as the first drug treatment for Alzheimer's.

After that request was rejected by the FDA's advisory panel, the agency suggested that Warner-Lambert apply for more limited marketing, the strategy used to release the AIDS drugs. Under the plan reviewed last week, up to 50,000 patients would have been given the drug under close scrutiny. But the advisory panel's vote on lack of efficacy made the plan moot for now. "There was concern that a very bad precedent could be set if the scientific standards were lowered," says Steven Ferris, a neurobiologist at New York University Medical Center, who chaired the committee. The group has recommended another study of tacrine's effectiveness. In the meantime, the FDA is hewing to the line that, as with any drug, benefits must clearly outweigh risks.

With reporting by Ginia Bellafante/New York and Dick Thompson/Washington