FDA broadens use of unproven AIDS drug.

FDA broadens use of unproven AIDS drug

The Food and Drug Administration and the National Institutes of Health last week agreed to an unprecedented widespread distribution of an unapproved AIDS drug, dideoxyinosine (DDI). At the same time, researchers sounded the death knell for dextran sulfate, aone-promising AIDS treatment, and cautioned against bypassing standard procedures for drug approval.

DDI's manufacturer, Bristol-Myers Co. of New York City, plans to distribute the drug free to thousands of AIDS patients who don't respond to or can't tolerate zidovudine (AZT) and who don't quality for clinical studies of DDI. AZT is the only AIDS drug approved in the United States.

Normally, drug testing for safety and efficacy takes about seven years, says FDA spokesman Brad W. Stone. AIDS patients have lobbied strongly for greater access to experimental therapies outside of drug trials (SN: 7/1/89, p.6).

In a pilot study of 56 patients, DDI showed promise of shorting up immune function by blocking replication of the AIDS virus, thereby boosting patients' CD4-positive T-lymphocytes -- the infection-fighting white blood cells destroyed by the virus (SN: 7/29/89, p.69). Researchers at the National Cancer Institute will now compare the drug's efficacy against that of AZT in clinical trials with 2,610 patients.

DDI is not risk-free. Some patients given high doses in the pilot study experienced limb pain and pancreatic swelling. But Robert Yarchoan of the National Cancer Institute, who helped develop DDI, told SCIENCE NEWS these conditions improved after patients stopped taking the drug. A daily dose of 500 to 750 milligrams appears effective and relatively nontoxic, Yarchoan says. The properties that make both DDI and AZT effective against the AIDS virus probably contribute to adverse reactions in patients, he adds. Both drugs are "chain terminators," binding to molecules in a growing chain of viral DNA and terminating the chain, preventing the virus from replicating.

Personal physicians will monitor patients who get DDI outside of clinical trials, reporting the results to researchers leading the clinical trials. It's too early to tell whether DDI will prove less toxic than AZT, which can cause anemia, Yarchoan says.

"There are people out there who seem to be failing on AZT or can't tolerate AZT and now have no therapy available to them. So to those people, death from AIDS is a very severe risk," he says.

The list of promising AIDS drugs got smaller after researchers reported in the Oct. 1 ANNALS OF INTERNAL MEDICINE that dextran sulfate was very poorly absorbed into the blood when administered orally during a clinical trial. Study coauthor Paul S. Lietman of the Johns Hopkins University School of Medicine in Baltimore says the large size and negative charge of dextran sulfate molecules might prevent them from crossing membranes and reaching into the brain and other tissues infected by the AIDS virus. Lietman and his colleagues are now studying the drug's efficacy when given intravenously.

In Japan, dextran sulfate is used as an anticoagulant and cholesterol-lowering agent. Although the drug isn't approved in the United States, FDA allows its importation for personal use. Many AIDS patients began importing oral doses of dextran sulfate after hearing it protected cultured T-lymphocytes from the AIDS-causing virus.

"I don't think it's compassionate to give greater access to unproven drugs," Lietman says. "More patients having access to [dextran sulfate] for the last year wouldn't have helped those patients or society or clinical research."

"Dextran sulfate is dead in most people's minds," agrees Donald I. Abrams of San Francisco General Hospital, who led an earlier clinical trial that revealed toxic side effects of the drug. Abrams says dextran sulfate "underscores the need for careful clinical trials."