Experimental Drug Available for Alzheimer’s

The Food and Drug Administration announced Monday that it will make a controversial experimental Alzheimer’s drug accessible to a limited number of patients while it is still under study.

The drug, Tacrine, or THA, would be the first made available to treat the progressive degenerative disease, which is the fourth leading cause of death among American adults.

The drug is not a cure for the ultimately fatal disease, which causes a gradual deterioration of mental processes, including memory. But it has helped some Alzheimer’s patients to improve their ability to think and function, according to its manufacturer, Warner-Lambert Co. of Morris Plains, N.J.

The drug also has been shown to cause liver damage.

Alzheimer’s disease afflicts about 4 million Americans and kills 100,000 annually. It strikes more than 10% of the population over age 65, and nearly 50% of those 85 or older.

Eventually, Alzheimer’s patients cannot care for themselves and require constant supervision. Over the course of the disease--which can often take years--the process typically reaps an enormous emotional and financial toll on the victim’s families and friends. The Alzheimer’s Assn., a national voluntary organization, estimates the annual cost of caring for the nation’s Alzheimer’s patients at $80 billion to $90 billion.

“I remember vividly a patient’s daughter saying to me that the death of the mind is the worst death of all,” said Dr. David A. Kessler, commissioner of the FDA. “The cruel and relentless nature of Alzheimer’s underscores the urgency of expediting important new therapies.”

The agency acted on the advice of a key FDA advisory committee, which recommended last July--with reservations--that THA be offered to Alzheimer’s patients if carefully controlled clinical trials of the drug continued at the same time.

“Caution needs to be the watchword,” Kessler said in an interview. “Patients on the drug have demonstrated a small improvement on psychological tests. It still remains to be seen whether that translates into a meaningful clinical benefit.”

There has been anecdotal evidence of dramatic gains in some patients, but Kessler said that those examples must be confirmed by study findings.

“We don’t base our decisions on anecdotal data. Our responsibility is to base our decisions on sound scientific evidence,” he said.

“There is a reason to believe the drug may work,” Kessler continued. “The definitive evidence is still not there. However . . . when there are no alternative therapies, it’s not fair to ask patients to wait in the interim.”

The new access program will be conducted at the same time as placebo-controlled clinical trials using much higher doses of the drug than have previously been studied, the FDA said.

THA has produced limited improvement at very small doses, and researchers hope that the drug will be more effective at higher doses. The first studies of the drug used the higher doses, but were quickly scaled back to lower doses after producing evidence that the drug caused serious liver damage.

“Our approval of the (access program) is based on the fact that there are also ongoing trials that will ultimately provide a definitive answer about the drug,” Kessler said.

Both the access program and the trials will use progressively higher doses of the drug and will exclude those patients who begin to experience liver problems as the doses increase.

“The hope is that by inching the dose up a little at a time, you’ll find out early those people who will get in trouble,” said Dr. Robert Temple, director of the FDA’s office of drug evaluation I. “The hope is that if higher doses can be tolerated, they will be more effective.”

The access program, which is expected to begin in February, will provide for the treatment of 3,000 patients beginning at a daily dose of 40 milligrams for six consecutive weeks, slowly increasing over several months to 120 milligrams, and possibly 160 milligrams, the agency said.

The program will be conducted by physicians selected by the company, but further details have not yet been worked out, the FDA said. To gather additional data on safety on the higher doses, patients will be strictly monitored, the agency said.

Stephen McConnell, senior vice president for public policy for the Alzheimer’s Assn., applauded the FDA’s decision.

“We want to make sure this drug is good for people and the evidence to date leaves that in question,” he said. “But we’re pleased the company is going forward with studies at the higher doses, and we’re pleased there also will be expanded access under controlled conditions.”

In certain limited cases, the FDA has allowed expanded access to experimental drugs that are promising, but unproved, in cases of serious illnesses where there are few or no treatment alternatives otherwise available.