[Letter to William H. Natcher from Bernadine Healy]

F '' EL: ER TELECOPIEPR,7 11 4- 6-' 12:."F'r' -0c1 4t...22., _;04 06 93 14:06 '0301 402 3522 MEDIA RELATIONS,Q003
Page 2 - The Honorable William H. Natcher
" Should other promising vaccine candidate products be
included for comparative purposes in a large-scale
clinical efficacy trial?
In addition, a gpl60 Trial Design Team was established to develop
a proposal for the design of an efficacy trial of gpl60 and other
therapeutic vaccine candidates. The design team developed a
protocol to serve as an experimental framework for the proposed
study and prepared a paper that addresses the key issues and options
concerning the design and conduct of the study. (Attachment 3)
These documents were reviewed at a January 28, 1993 meeting of a
Subcommittee of the gpl60 Panel and revised to incorporate
several changes recommended by the Subcommittee to delineate
priorities within the plan and to keep the clinical trial within
the 520 million budget designated by Congress. (Attachments 4 & 5)
On the basis of the deliberations of the Panel and its
subcommittees--and relying on non-traditional scientific criteria
and other considerations that arise from the unique nature of the
HIV epidemic-'the gp160 Panel recommended that the funds
designated in the Department of Defense appropriation should be
used to begin a large-scale clinical efficacy trial of
therapeutic HV vaccines. However, the Panel recommended that:
* The large-scale clinical trial of a therapeutic vaccine for
HIV should be designed to study several products, including
the MicroGeneSys gp160 candidate vaccine and other vaccine
candidates from among those now being developed by
Genentech, Chiron-Biocine, ImmunoAG, and Immunization
Products Limited.
* The large-scale clinical trial should not be limited to
military personnel and veterans, and should include a
broad-based civilian population group, extending to
underrepresented minorities, injecting drug users, and
others among whom the incidence of HIV infection is high.
* The cliiical trial should focus on HIV-infected individuals
whose CO4+ T cell counts range between 200/ms3 and 500/ms.
Expansion of the trial to include individuals with less
than 200/mm should be contingent on results from current
Phase I studies of the vaccine candidates indicating
whether the products are appropriately immunogenic.
* The primary objective of the trial--determining the
clinical efficacy of therapeutic vaccines in HIV-infected
individuals--should be assessed by measuring progression to

marker diseases and mortality. A secondary objective of
the trial, evaluating the correlation between CD4+ T cell
counts and clinical outcomes, should also be met (with a
focus on participants with CD4+ T cell counts between
200/mm and 500/mm).