Note: The following statement was developed by many people, collectively calling themselves the Protease Consensus Coalition. It has been signed by 61 organizations, including ACT UP/New York Treatment and Data Committee, AIDS Project Los Angeles, AIDS Research Alliance (formerly Search Alliance), AIDS Treatment News, Being Alive (Los Angeles and San Diego), Committee of Ten Thousand, Log Cabin Republicans, Mothers' Voices, National Association of People with AIDS, Project Inform, and the San Francisco AIDS Foundation. Over 100 individuals have also signed on. Organizations and individuals can obtain a copy or sign the statement by sending a fax to the Linda Grinberg Foundation, 310/471-4565, which is collecting signatures for this project.

Consensus Statement on the Accelerated Approval of Protease Inhibitors * Overview Access to protease inhibitor drugs now in development represents the best hope for delaying disease progression for tens of thousands of people living with HIV and AIDS who have exhausted the limited benefit from currently approved antiviral therapies. As a class, these drugs have demonstrated both lower levels of toxicity and significantly increased levels of antiviral activity, even in people with advanced disease.

The benefit of these drugs may be limited due to the development of drug resistance, a problem common to all currently approved antiviral compounds. While it may take years of additional study to determine the optimal use of protease inhibitors, this certainly should not delay prompt access to this therapy by people in urgent need and those who wish to add them to their arsenal of HIV medications. Any further delay in the availability of these drugs is a moral affront to the rights of people with HIV/AIDS and their healthcare providers.

* Compassionate Use/Salvage Therapy We demand that both sponsors and the Food and Drug Administration take a more compassionate stance and cooperate to make promising compounds like these available in "salvage programs" after the first evidence of safety and surrogate marker activity. These compassionate access programs should routinely make drug available, prior to accelerated approval, for those people who have failed existing therapies and risk near-term danger of death or life-threatening infections.

The development of this class of drug must take into consideration its unique ability to provide benefit to the acutely compromised segment of the HIV-infected population. Availability of salvage strategies is of the highest priority for people living with HIV. There is no logical or moral reason to withhold these drugs from people with advanced illness, people whose lives hang in the balance. Currently, the compounds from Abbott, Merck and Roche are qualified, by any humane standard, for compassionate use.

* Accelerated Approval Protease inhibitor compounds should be licensed for accelerated approval as soon as possible. FDA approval of these compounds should be based on existing regulations governing accelerated approval of new drugs for life- threatening illnesses: (1) Clear evidence of benefit on surrogate markers has been demonstrated; (2) Principal toxicities have been defined; (3) Longer-term development plans have been initiated designed to determine the drugs' usefulness in promoting clinical and survival improvements as part of a medical strategy for coping with HIV infection.

These conditions have been met, or nearly met, by a number of the existing candidate protease inhibitor compounds, and we urge their sponsors to file application for accelerated approval no later than the 2nd quarter of 1995. Currently the compounds from Abbott, Merck, and Roche qualify by showing far superior antiviral activity than any other drug granted approval under this regulation.

* Resistance and Drug Interactions As with all antivirals, the development of drug-resistant strains of virus while using these compounds may warrant additional considerations. To address this concern, sponsors should also be required, prior to accelerated approval, to present meaningful data on: (a) the speed and levels of resistance encountered; (b) the degree of cross-resistance found with other protease- inhibitor compounds; (c) the interaction of the compound with other commonly used anti-HIV medications; (d) bioavailability.

* Summary Any effort to withhold access to promising protease inhibitor compounds is contrary to the interests of HIV-infected people, inconsistent with the Accelerated Approval regulations, and scientifically unwarranted. The long history of the development of the earlier generation of antiviral drugs clearly demonstrates that it is possible to continue conducting clinical trials of compounds, long after their marketing approval.

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