Alzheimer’s Drug Backed for Approval

A Food and Drug Administration advisory board unanimously recommended marketing approval Thursday for tacrine, the first drug shown to be effective for Alzheimer’s disease, which affects as many as 4 million Americans.

Approval of the drug requires action by the FDA itself, but the agency normally follows the recommendations of its advisory panels. The drug, which would be the first Alzheimer’s medication sanctioned by the FDA, could be available to patients within a couple of weeks, and certainly within two or three months, said officials of the FDA and Warner-Lambert Co., which manufactures tacrine.

Although previous trials of the drug had proved inconclusive and the board had twice turned down marketing requests, new data indicated that the drug can partially reverse the loss of mental function associated with the disease.

The panel noted that the drug, also known as THA, does not work for everyone and that it has the potential to cause severe side effects. One out of four patients who take the drug are susceptible to severe liver damage, but that damage is reversible if they stop taking the medication. Despite this side effect, the group concluded that it should be made available to patients because they have no alternatives.

“It does come down to a matter of conscience,” said Dr. Dennis Choi, a panel member who is chairman of the department of neurology at Washington University School of Medicine in St. Louis, Mo. “I believe the drug is reasonably safe. I don’t see why someone shouldn’t have the ability to combat a life-threatening disease.”

The recommendation also represents a vindication for Dr. William K. Summers, who discovered the drug while working at UCLA. His initial study on the drug, reported in 1986, was heavily criticized by the FDA and many of his colleagues for being overly optimistic and poorly designed.

Summers, who is on a sabbatical from his private practice in Arcadia to help promote FDA approval of the drug, said Thursday, “I am just as excited as all get-out. This is a great day for Alzheimer’s patients and their families.”

Alzheimer’s disease primarily strikes people over 65 and is characterized by memory loss, disorientation, depression and deterioration of bodily functions. It is ultimately fatal, causing about 100,000 deaths in the United States each year. Until now, there was essentially no treatment to slow the disease, although physicians have been able to treat specific symptoms.

The cause of Alzheimer’s is still unknown, but symptoms are produced by the death of brain cells that secrete acetylcholine, a neurotransmitter essential to many thought processes. Tacrine blocks the function of enzymes that normally break down excess acetylcholine, thereby making more of the neurotransmitter available to brain cells.

The new data came from a 30-week study of tacrine conducted on more than 600 Alzheimer’s patients at 33 U.S. medical centers. These studies, at the recommendation of the FDA advisory panel, used higher doses of tacrine over a longer period of time than in previous research.

At the highest dosage levels, the patients “showed significant evidence of benefit by neuropsychological testing and improvements in memory and cognitive function,” according to Dr. Martin Farlow, a neurologist at the Indiana University Medical Center who participated in the study. At lower doses, he added, “there was improvement in some cases, but the degree of improvement was not as great.”

Farlow noted that the panel “spent considerable time wrestling with the issue of quantifying improvement,” but ended up not attempting to do so. “The final thought was that there is an effect, but the actual benefit is best judged by the patient’s physician and family.”

But Nancy Smith, an FDA statistician who analyzed the data from the new trial, said the intellectual performance of the patients receiving tacrine improved by 5 points on a 0-to-70 scale commonly used in evaluating Alzheimer’s patients.

Dr. Richard Mohs, a neurologist at the Veterans Affairs Medical Center in the Bronx, N.Y., noted that there was no “miracle” with tacrine, as Summers had suggested in his first studies with the drug, but that there was benefit.

“You don’t get people back to where they were 10 years ago,” Mohs said, “but you do have people with significant improvement based on clinical observation.”

Farlow also noted that no increase in the incidence of liver problems was observed in the patients receiving the highest doses of tacrine. All patients were monitored weekly to test for impairment of liver function, and it seems likely that such monitoring will be recommended, or required, when the drug is marketed.

“The side effects overall were quite manageable,” Farlow said.

Summers said he believes his initial, highly promising results will now be replicated. “When (tacrine) gets in the hands of common physicians, they will find that it does pretty much what we said it would.”