AIDS Drug OK Expected Before Test Completion

Federal health officials are expected to approve widespread distribution of a promising new antiviral AIDS drug before human studies have proved it effective against the deadly disease, knowledgeable sources said Wednesday.

The Food and Drug Administration is expected to announce within several days that it will release the drug dideoxyinosine, or DDI, for use by patients who cannot tolerate the approved drug AZT and who are ineligible to participate in DDI research trials, the sources said.

FDA scientists are studying the most recent data submitted by the drug’s manufacturer, Bristol-Myers Co., before making a final decision, which could come Friday or early next week, the sources said.

DDI would be distributed as a “treatment IND,” or investigational new drug, which would allow its use by patients before it is approved for marketing.

What would make this decision highly unusual, however, is that DDI would be released before human studies have demonstrated that it has had an impact on the disease.

Traditionally, a treatment IND is not approved until “Phase II” clinical trials have been completed or are well under way. Phase I studies examine only whether a drug is safe. Phase II and III studies determine the best dose of the medicine and whether the drug is effective against an illness or a condition.

Phase I studies have been completed on DDI, but Phase II trials have not yet begun.

Shows Willingness

The decision to make the drug available underscores an increased willingness by the federal government to speed patient access to promising experimental drugs for life-threatening conditions.

Intense pressure from AIDS activists, coupled with a gradually changing philosophy among federal regulators, has resulted in a new approach to delivery of potentially valuable drugs to desperately ill patients who, in the past, have had few or no therapeutic alternatives.

In the case of life-threatening illnesses such as AIDS, some of the rigorous rules that once applied to the distribution of new drugs have been relaxed.

DDI would be made available to patients with fully developed AIDS and ARC, or AIDS-Related Complex, who are medically unable to take AZT and who do not qualify to participate in formal trials to study DDI’s effectiveness, according to agency sources.

AZT, the only other antiviral AIDS drug currently available, has proved toxic in many patients with fully developed AIDS, frequently causing severe anemia that requires blood transfusions.

Others to Receive Drug

In addition, DDI would be made available for “compassionate use” among a smaller group of AIDS patients for whom AZT has failed and “who are at death’s door,” sources said.

Bristol-Myers would provide the drug free of charge, sources said.

Three Phase II trials are planned to study whether DDI is effective, the sources said. None of the trials will use a placebo, a medically worthless pill administered to a control group of patients, sources said.

Instead, two of the three studies will compare patients taking DDI to a control group taking AZT. One control group will consist of patients who have never taken AZT or who have taken it for less than three months, sources said. The second control group will use individuals who have taken AZT for more than a year.

The third Phase II trial will study AIDS patients who cannot tolerate AZT and will compare a low dose of DDI to a higher dose of the drug, sources said.

Believed to Be Effective

Although so far, scientists have studied DDI in humans only to determine if it is safe, many have said privately that they believe it to be just as effective as AZT against the disease, but at lower dosages, meaning that there would be less chance of dangerous side effects.

To support this view, they cite preliminary evidence that DDI boosts the concentration of disease-fighting T-4 white blood cells. Higher concentrations of such cells, which are attacked by the AIDS virus, appear to increase an AIDS patient’s chances for survival.

Safety studies have shown that at high doses, DDI has the potential to cause dysesthesia, a numbness or pain in the feet; burning in the hands and fingers; and pancreatitis, an inflammation of the pancreas.

In July, in an action that took many federal health officials by surprise, Bristol-Myers said that it would make DDI available at no cost to AIDS patients before testing was completed to prove its effectiveness.

The decision was hailed by AIDS activists, who had been pressuring the company to make the drug available. But it reportedly irritated federal health regulators, who said that the company had overstepped its jurisdiction by making such a promise.

Legally, only the FDA has the authority to sanction distribution of a drug to individuals who are not part of formal human studies.

Proposes ‘Parallel Track’

At the time, Dr. Anthony S. Fauci, director of AIDS activities for the National Institutes of Health, proposed creation of a “parallel track” of clinical trials for experimental AIDS drugs to provide an alternative for patients who were ineligible for formal trials.

DDI is expected to be the first drug distributed under that process but details of how the parallel track plan will work have not yet been made final.

AZT, or zidovudine, is the only antiviral AIDS drug approved so far for marketing. It was approved for sale in March, 1987, but has been widely used since September, 1986, when the results of Phase II studies showed that the drug had a dramatic impact on prolonging life.

AZT has caused serious side effects in patients with fully developed AIDS. Studies have shown it to be far less toxic in individuals who are infected with the AIDS virus but who have not yet developed symptoms of the disease.