AEGiS-GMHC: ddI/ddC Licensing Update

Important note: Information in this article was accurate in 1991. The state of the art may have changed since the publication date.

ddI/ddC Licensing Update

TREATMENT ISSUES--The GMHC Newsletter of Experimental AIDS Therapies - Vol. 5, No. 1 - January 10, 1991
David Gold

In the past two years, AIDS activists have successfully negotiated with the manufacturers of two experimental antiviral drugs, ddI and ddC, to develop expanded access programs. These programs allow for access to the drugs before they become fully licensed, and are for people who do not qualify for clinical trials. The expanded access programs have provided treatment options to thousands of people whose conditions were deteriorating in spite of treatment with AZT. Many other people, however, do not meet the specific medical criteria required to obtain ddI and ddC, even certain individuals who can no longer take AZT due to toxicity or resistance. Now, activists are beginning to focus their energies on obtaining licensing approval for both ddI and ddC, so that everyone who might benefit from these drugs will be able to obtain them.

History

In November 1989, Bristol Myers-Squibb, the manufacturer of ddI, under pressure from AIDS activists, initiated an expanded access plan. Individuals who were intolerant to, or had failed AZT, and who were unable to qualify for clinical trials, were given access to the drug through their physician. As of December 1990, over 13,000 individuals have obtained ddI through this plan.

Hoffman-La Roche, manufacturer of ddC, first announced an expanded access program for its drug in June 1990. Because the plan limited the number of patients to be enrolled in the trial, and also made failure of AZT and ddI a requirement for entry, it was quickly dubbed "a limited access plan" (24). In September 1990, Hoffman-La Roche yielded to pressure from a nationwide coalition of more than 160 AIDS organizations, researchers and physicians, including ACT UP New York, GMHC, and Project Inform. The manufacturer agreed to provide ddC to an unlimited number of individuals who had failed or become intolerant to AZT.

As of this date, Hoffman-La Roche claims to have enrolled close to 1,000 people in its ddC access plan. Nevertheless, there are still substantial problems with the plan, which effectively limits the number of people gaining access to ddC. In order to enroll patients in the program, Hoffman-La Roche requires physicians to obtain approval from local Institutional Review Boards (IRBs). An IRB is a hospital committee that decides if an unlicensed drug may be used in its hospital. In comparison, Bristol-Myers Squibb obtained a "blanket" IRB approval from the FDA for its ddI program, eliminating the need for hospitals to make separate, internal decisions. Hoffman-La Roche also requires an overwhelming amount of paperwork to enroll patients in the ddC program, discouraging some physicians from trying to obtain ddC for their patients. More information about the ddC access plan is available by calling 1-800-HIV-21-ddC.

Licensing Campaigns

Activists will be meeting with Hoffman-La Roche to discuss concerns about the limitations of the ddC expanded access program, in January 1991. Other agenda items for the meeting will include: release of preliminary results from the ddC trials; progress on a New Drug Application for ddC (the paperwork required by the FDA for full licensing of a drug); and the company's plan for developing protease inhibitors, a new class of drug that interrupts HIV replication differently than do AZT, ddI and ddC.

The campaign to gain rapid licensing approval for both ddI and ddC is crucial for many persons with HIV and AIDS. For tens of thousands of individuals, AZT is simply too toxic or it is no longer effective due to the development of resistance. Additionally, too many people do not meet the tightly-drawn inclusion criteria for the ddI and ddC access plans. For example, one of the criteria for a diagnosis of "AZT intolerance" is that the patient must become severely anemic on two occasions. Many physicians, however, prefer to give their patients blood transfusions rather than allow them to become so anemic as to manifest symptoms such as severe weakness or dizziness. As a result, many people who cannot continue on AZT will also not qualify for expanded access, and so are left with no effective antiviral therapy option.

Activists also point out that more is known about the efficacy and toxicity of ddI and ddC at this point than was known about AZT when it was approved. In addition, many researchers and clinicians believe that the safest and most effective use of nucleoside analogs (the class of drug which includes AZT, ddC and ddI) is with low-dose combinations. Combining AZT and ddC, either in alternating or concurrent doses, is believed to limit toxicity, delay or prevent resistance, and possibly act synergistically to achieve greater efficacy (25,26).

Conclusion

Given all the factors, activists believe that enough is known about the safety and efficacy of both ddI and ddC to make them available by prescription. Certainly, much more is known about the safety of these two drugs than was known about AZT when it was approved in 1987. The most contentious issue now is how to measure ddI's and ddC's effectiveness by objective laboratory values (or "surrogate markers"). But many clinicians have provided testimony about their patients' improvement while taking these drugs (27) and clinical trials results to date support such claims (28,29). It is worth noting, however, that much of the data on ddC remains unpublished. Unless more papers appear in medical journals, it will be difficult for clinicians who have not followed community publications to use the drug when it is licensed.

Patients ought to have the right to make informed choices with their physicians about which treatment regimen to pursue. Without access to ddI and ddC, many patients find themselves in a predicament similar to that faced by people with symptomatic HIV infection before AZT became available by prescription.

Copyright (c) 1991 - Gay Men's Health Crisis, Inc. All rights reserved. Permission granted for non-commercial use. Non-commercial reproduction is encouraged. Distributed by AEGIS, your online gateway to a world of people, knowledge, and resources. Direct Dial: v.34+: 714.248.2836; v.120/ISDN: 714.248.0433 Internet: telnet:aegis.com www: www.aegis.com

910110
GM050103

Copyright © 1991 - Treatment Issues. Reproduced with permission. Treatment Issues is published twelve times yearly by GMHC, Inc. All rights reserved. Noncommercial reproduction is encouraged. Subscription lists are kept confidential. GMHC Treatment Issues, The Tisch Building, 119 West 24th Street, New York, NY 10011 fredg@gmhc.org http://www.gmhc.org

AEGiS is made possible through unrestricted grants from Boehringer Ingelheim, Elton John AIDS Foundation, iMetrikus, Inc., John M. Lloyd Foundation, the National Library of Medicine, and donations from users like you. Always watch for outdated information. This article first appeared in 2003. This material is designed to support, not replace, the relationship that exists between you and your doctor.

AEGiS presents published material, reprinted with permission and neither endorses nor opposes any material. All information contained on this website, including information relating to health conditions, products, and treatments, is for informational purposes only. It is often presented in summary or aggregate form. It is not meant to be a substitute for the advice provided by your own physician or other medical professionals. Always discuss treatment options with a doctor who specializes in treating HIV.

Copyright ©1980, 2003. AEGiS. All materials appearing on AEGiS are protected by copyright as a collective work or compilation under U.S. copyright and other laws and are the property of AEGiS, or the party credited as the provider of the content. .