Halted Alzheimer’s Drug Study to Resume

A national study of a highly touted experimental drug for Alzheimer’s disease, suspended in October after some participants developed serious liver problems, is likely to resume in the next several weeks, The Times has learned.

The U.S. Food and Drug Administration and the Warner-Lambert Co., a Morris Plains, N.J., pharmaceutical company, are putting the finishing touches on the revised procedures, which will include reduced doses of the medicine and closer monitoring for side effects.

“I am the one who is going to sign off on it (approve the request to resume the study), and there is very little reason not to sign off on it,” the FDA’s Paul Leber said in a telephone interview.

Leber, director of the FDA’s division of neuropharmacological drug products, said that the study could be restarted because the liver side effects that developed in eight patients had slowly reversed after the medication was discontinued and there was no evidence of long-term harm.

“I can’t officially confirm it for you,” said Marshall E. Molloy, a spokesman for Warner-Lambert. “(But) I would say there will likely be an announcement in the very near future.” Molloy said Warner-Lambert was in the process of asking the FDA for formal approval to renew the tests, as well as seeking approval for the revised testing procedures from participating medical centers around the country.

The drug, tetrahydroaminoacridine, or THA, gained nationwide attention in November, 1986, when a team of Los Angeles researchers reported in the New England Journal of Medicine that THA had markedly improved the memory and living skills of about a dozen Alzheimer’s patients for a year or more. Immediately, patients, family members and physicians bombarded the investigators and the government, requesting the medicine.

But in 1987 THA became mired in controversy. The 300-patient national study, designed to confirm the earlier findings, was started, with much fanfare, in September. But weeks later, the study was suddenly halted, after eight of about 35 patients who had received high doses of the drug developed abnormal “liver function” blood test results.

The initial Los Angeles study was also criticized by other investigators for technical flaws and for an arrangement in which patients who received the experimental treatment had to pay the costs, up to $12,000 a year. Traditionally, the expense of such treatment is borne by a study’s sponsors.

In July, the FDA began an audit of Arcadia psychiatrist Dr. William K. Summers, the principal author of the Los Angeles study.

So far the FDA probe has found numerous deficiencies, including missing lab test results and inadequate documentation to back up the researchers’ assertions of “dramatic” improvements, according to agency documents. The FDA has also rebuffed plans to expand the Los Angeles study from 40 to 200 patients.

Importance Downplayed

In an interview Tuesday, Summers downplayed the significance of the ongoing audit, stating that the missing test results and documentation had “nothing to do” with the study’s overall conclusion--that THA is effective.

“We don’t feel that the integrity of the paper was truly shaken by that inquiry,” Summers said. “We stand by our findings.” For example, Summers said that FDA officials actually had 55% of the approximately 350 pieces of information that were said to be missing and that an additional 28% of the requested data had been found.

The two-year national THA study is funded by Warner-Lambert, the National Institute of Aging and the private Alzheimer’s Disease and Related Disorders Assn. When it is resumed, it will be conducted at 17 medical centers.