Firm to Offer AIDS Drug Free in Critical Cases

NEW YORK — In a decision that AIDS activists hope will lead to significantly widened access to experimental AIDS drugs, Bristol-Myers Co. pledged Thursday to provide “compassionate use” of its drug DDI, or dideoxyinosine, to any AIDS patient who cannot participate in formal trials but “for whom the drug is critical.”

The new program will begin in September and will run parallel to Phase 2 trials designed to test the antiviral drug’s effectiveness as an AIDS therapy. The company said the plan conforms to Food and Drug Administration regulations and appears to fit with the innovative dual-track drug-testing program outlined last month by Dr. Anthony Fauci, National Institutes of Health AIDS research chief.

Bristol made its announcement here after weeks of behind-the-scenes negotiations with government officials and members of the AIDS advocacy group ACT UP--and on the same day as three dozen Canadian AIDS activists staged a demonstration at the drug giant’s Toronto office. Six members of the group AIDS Action Now were arrested for trespassing.

“This could be the start of a historic shift . . . in which the AIDS community and the pharmaceutical companies sit down and cooperate with one another,” said Mark Harrington, who negotiated with Bristol on behalf of ACT UP.

Harrington added, however, that “it all depends on how they define the word critical. “ In the past, he noted, some companies have restricted compassionate-use distribution to patients who are within days or weeks of death rather than making drugs available in earlier stages of an illness.

Cousin of AZT

DDI, which is taken orally, is a chemical cousin of Burroughs-Wellcome’s drug AZT, the only antiviral drug currently approved by the FDA for use against the human immunodeficiency virus that causes AIDS. Bristol bought worldwide marketing rights to DDI from the drug’s developer, the National Cancer Institute, in January, 1988.

In Phase 1 toxicity trials of the drug at the National Cancer Institute and other medical centers, DDI suppressed production of the virus and led to what scientists said were statistically significant increases in T-4 helper cells, the white blood cells that are key sentinels of the immune system.

More important, DDI appeared to be well-tolerated by AIDS patients. AZT, on the other hand, is so toxic that some have estimated that up to 50% of AIDS patients have been forced to reduce or eliminate their use of the drug.

“DDI is the only drug we have now for people who are intolerant of AZT, or for those who develop strains of the virus that are resistant to AZT,” said Dr. Mathilde Krim, founding chair of the American Foundation for AIDS Research. “The company is to be praised for its moral leadership in the face of this public health emergency.”

“For the first time, we can really talk about giving people an antiviral drug other than AZT,” said Dr. Ellen Cooper, director of the FDA’s division of antiviral drugs.

Free to Patients

Under the plan, details of which remain to be worked out, Bristol is expected to provide the drug free. In return, said Thomas D. McCann, vice president for corporate communications, “we would hope to collect data” to supplement data gathered in the more rigorous formal trials for eventual submission to the FDA.

Bristol said it will begin formal trials and compassionate-use programs in both the United States and Canada by September, 1989, after regulatory officials review and accept the company’s Phase 1 safety data.

By collecting data from the compassionate-use patients, Bristol hopes to overcome one of the biggest problems drug companies have encountered in the past under such programs. Drug industry observers believe that FDA licensing of Syntex Corp.’s drug ganciclovir was delayed by several years because the company gave so much of it away on compassionate use to treat AIDS-related cytomegalovirus retinitis, an infection that can cause blindness.

Although the compassionate-use program will probably add millions of dollars to the company’s drug development expenses, “if DDI proves itself to be superior to AZT, it will be a very nice product for Bristol,” said Drexel Burnham Lambert drug analyst David Lippman. Annual revenues, he estimated, would be “in the hundreds of millions of dollars.”

FDA licensing of the drug could also provide a measure of financial relief to employers, insurance companies and government programs that currently pay up to $8,000 a year per patient taking AZT.

Control on Price

Under the terms of the National Cancer Institute’s contract with Bristol, the government can force Bristol to license the drug to another company if Bristol does not set a reasonable price for the drug. A Bristol spokesman said it is premature to discuss the drug’s pricing.

The struggle over access to DDI represents a new phase in the efforts of AIDS patient-advocates to obtain promising drugs.

“Hallelujah,” added ACT UP’s founder, playwright Larry Kramer. “I pray that Bristol’s magnificent example will be duplicated by the manufacturers of numerous other life-saving drugs.”

The company’s announcement capped a week in which some government regulators feared that Bristol seemed paralyzed by steadily mounting pressure from the activists and conflicting signals from the FDA and the NIH involving terminology and general ground rules of the program.

Ultimately, Bristol chose to call the plan a “compassionate-use” program--language favored by the FDA--rather than using the “parallel track” terminology embraced by the NIH.

Whatever the label, said Bristol spokesman Jerry Parrott, “we are committed to the idea conceptually” and “we are working with the government right now” to develop the details of the program.”

“Any patient who does not meet the criteria for Phase 2 clinical trials, but for whom DDI is critical, would receive the drug under this plan,” the company said. Spokesmen for Bristol said they could not estimate how many patients would receive the drug under the trials and compassionate-use programs, although it would certainly be in the thousands.

Effective Dosage

The drug has been used by 90 patients during Phase 1 trials. In addition, an undetermined number of people have purchased an alleged chemical equivalent through the flourishing AIDS treatment underground. Based on Phase 1 data, a safe and effective dose appears to be two grams per day, according to sources within the Public Health Service.

Bristol spokesman Parrott insisted that the company was not swayed by the Toronto demonstration or the threat of similar actions at its Park Avenue headquarters in New York, where ACT UP has in the past marshaled more than 3,000 people for major demonstrations.

Still, Harrington said, “our Canadian friends gave Bristol a foreshadowing of what was in store for them” if the company refused to release DDI. Activists also raised the possibility of a boycott of Bristol’s consumer products, which include Bufferin, Ban and Windex.

Other lobbyists for the program included government officials such as Fauci and Dr. Neil Schram, a Harbor City physician and head of the American Assn. of Physicians for Human Rights committee on AIDS.

“The rules have just been rewritten,” Schram said Thursday. “It is a remarkable thing.”