Protease Inhibitor Consensus Statement



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.