Important note: Information in this article was accurate in 1989. The state of the art may have changed since the publication date.
Food and Drug Administration, U.S. Department of Health and Human Services - September 28, 1989
Brad Stone/FDA (301) 443-3285; Elaine Baldwin/NIAID (301) 496-5717
"This plan offers some additional options for people with AIDS, and particularly for the thousands of AIDS patients who cannot tolerate therapy with AZT," Dr. Sullivan said. "This plan for expanded testing and earlier availability of ddI, developed through the cooperation of several Public Health Service agencies and Bristol-Myers, reaffirms our commitment to speeding both the development and the availability of promising new drugs for patients with AIDS whenever possible."
Assistant Secretary for Health James O. Mason, M.D., Dr.P.H., commended FDA and NIH for their work in developing and implementing these protocols for ddI. "This successful collaboration among FDA, NIH, and Bristol-Myers is indicative of the Public Health Service's continuing efforts to combat AIDS," he said.
HHS is developing procedures to expand availability of investigational therapeutic agents through a parallel track mechanism. Today's announcement that ddI will be available through a Treatment IND and open safety protocol is consistent with the parallel track concept and is an interim measure to make a promising investigational therapy available for people with AIDS who do not have satisfactory treatment options.
Dideoxyinosine, which was initially developed by Samuel Broder, M.D., and Robert Yarchoan, M.D., at the National Cancer Institute (NCI), is one of a group of drugs, including zidovudine, that inhibit replication of the AIDS virus. Phase 1 safety trials of ddI were recently completed by NCI and ACTG investigators at the University of Rochester and New York University.
These studies showed that, while ddI appears promising, it has toxicities related to the dose taken; thus, its use requires careful monitoring. Although studies reported earlier this year indicated that ddI could be tolerated by most AIDS patients, more recent data indicate that some patients taking ddI, particularly at higher doses, have experienced painful nerve damage to the feet and, less commonly, damage to the pancreas. These toxicities appear to be reversible if detected early and if the drug is discontinued. The protocols announced today take these most recent data into account by selecting doses that appear to be well tolerated and have evidence of activity against the AIDS virus.
Despite the promising early results with ddI, it is important to emphasize that zidovudine is the only drug with proven efficacy for the treatment of patients with AIDS and advanced ARC.
Three Phase 2 clinical trials of ddI in people with AIDS and ARC will be conducted by NIAID's nationwide network of ACTG units. The studies are designed to provide definitive data on whether the drug is useful in treating patients with AIDS or ARC. Protocol 116 will be a randomized, double-blind comparison of ddI and zidovudine in 1,500 persons, 900 of whom have had little or no previous treatment with zidovudine and 600 of whom have taken zidovudine from 2 months to a year. Protocol 117 will compare ddI and zidovudine in 750 persons who have been on zidovudine for at least 1 year. Protocol 118, which will include 360 persons with AIDS and ARC who cannot take zidovudine because of serious drug toxicity, will compare 3 different doses of ddI.
Results of the Phase 1 studies served as the basis for granting Treatment IND status. The Treatment IND mechanism was established by FDA to allow patients suffering from serious or life-threatening conditions for which there is no satisfactory treatment to obtain promising experimental drugs while research continues.
Under the Treatment IND, AIDS patients who have experienced severe anemia or other dose-limiting adverse reactions to zidovudine will be eligible to receive ddI through a program administered and funded by Bristol-Myers. The patients on this protocol will be monitored by their physicians for evidence of toxicity also.
In addition, an open safety protocol sponsored by the company, will allow ddI to be studied in AIDS patients whose disease has progressed substantially despite zidovudine therapy. Entrance criteria for the protocol will continue to be evaluated, and appropriate adjustments made, as data are accumulated, and more information on safety and efficacy becomes available.
The operation of the clinical trials, Treatment IND, and open safety protocol will be closely monitored so that the most current information about the drug is provided to patients, physicians, and researchers. The continuation of the Treatment IND and open safety protocol depends on satisfactory results with respect to the drug's safety and efficacy as well as adequate enrollment in the clinical trials.
Although Bristol-Myers is not charging for the cost of the drug in any of these programs, there are likely to be physician and laboratory charges associated with receiving ddI through either the Treatment IND or open safety protocols.
FDA Commissioner Frank E. Young, M.D., Ph.D, said, "The epidemic of AIDS is extraordinary, and must be met with extraordinary measures. Since ddI is still an experimental drug, it must be tested carefully and must demonstrate safety and efficacy before it can be approved. We believe, however, that it is important to offer the drug now to people with AIDS for whom the standard treatment of zidovudine is not an option even though there are some potentially serious side effects."
Anthony S. Fauci, M.D., NIAID Director and Associate Director for AIDS Research at the NIH, said, "I am pleased that ddI will be entering Phase 2 clinical trials to determine definitively its efficacy in people with AIDS and ARC, and to gain further information regarding safety and optimal dosage. In addition, it is appropriate that simultaneously the drug is being made more widely available to those individuals who cannot take AZT or whose disease has substantially progressed despite AZT therapy."
Physicians, patients, and others interested in the clinical trials, Treatment IND or open safety study can call 1-800 TRIALS-A, a toll-free service offering information about AIDS clinical trials from 9 a.m. to 7 p.m., Eastern Time, Monday through Friday.
Physicians interested in details of the Treatment IND and open safety protocol can call the Bristol-Myers toll-free number at 1-800-662-7999 daily from 8 a.m. to 8 p.m., Eastern Time. The company will immediately begin processing applications from physicians for their patients for the Treatment IND and open safety protocol. Bristol-Myers estimates that physicians with patients eligible for participation in these protocols should begin to receive the drug in about 2 weeks.
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SOURCE: Food and Drug Administration (FDA).
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