PR Newswire - November 16, 1995

Treatment with PMPA was not associated with any observed toxicities in this study. SIV infection in primates is an animal model for HIV or human immunodeficiency virus infection, the causative agent of AIDS in people.

Data from this preclinical study, published in the November 17 issue of Science, demonstrate that one course of daily PMPA treatment for four weeks provided 100 percent protection from any detectable signs of SIV infection in the primates for up to one year, which was the duration of study follow-up. In contrast, all primates in the control group, which did not receive treatment with PMPA, showed signs of SIV infection within one to three weeks following exposure to the virus.

All primates in the study were monitored for changes in viral activity, immune system responses and clinical status throughout the study. Some of these tests represent the most sensitive assays available to detect viral infections and included screening for SIV antibodies in blood and plasma, detection of SIV viral DNA by PCR and biopsies of lymph node tissues, where the virus is known to reside or "hide" in a latent state.

"This is another example of the exceptional in vivo potency of nucleotides as compared to nucleosides," said Norbert Bischofberger, Ph.D., co-author of the study and Vice President for Research at Gilead Sciences.

Study Design

In the study, PMPA was administered subcutaneously to macaque monkeys starting either before or after inoculation with the SIV virus. The primates in the control group did not receive any treatment and were inoculated with the same amount of virus, which was approximately ten times the amount of SIV known to cause infection.

The study included a total of 35 macaques, 10 of which were in the control group. A total of 25 macaques received treatment with PMPA beginning 48 hours before, 4 hours after or 24 hours after inoculation with SIV. The macaques in the treatment groups received 30 mg/kg of PMPA subcutaneously in single, daily doses for 28 to 30 days.

While PMPA was the only antiretroviral therapy administered in this study, the authors did compare PMPA's activity to results obtained from other SIV studies in this model. One such comparison found PMPA to be significantly more efficacious and better tolerated than AZT (also known as zidovudine), a currently approved HIV therapeutic. For example, the historical data demonstrate that treatment with AZT protected only 6 percent of the primates when dosed before exposure and 0 percent when dosed four hours after exposure to the SIV virus.

The study was led by Che-Chung Tsai, Ph.D., D.V.M., from the University of Washington Regional Primate Research Center, Primate Field Station in Medical Lake near Spokane, WA. Additional collaborators include colleagues of Dr. Tsai from the University of Washington and researchers representing Gilead, the National Institute of Allergy and Infectious Diseases' Division of AIDS and the National Cancer Institute.

PMPA - Potential Applications

PMPA is currently in the preclinical phase of testing, and its potential activity against HIV in humans has not yet been studied. The data published in the November 17 issue of Science represent the first scientific publication of PMPA's activity in primates and potential utility for the treatment of HIV and/or the prevention of HIV infection in cases of known exposure. For example, the authors reported that based upon the disclosed data, PMPA may have potential applications in the treatment of healthcare workers or others accidentally exposed to HIV, including newborns exposed from an infected mother in maternal-fetal transmission.

The authors report that additional preclinical studies in the macaque model are ongoing to assess and define the upper limits of PMPA's protective nature when dosed at time points longer than 24 hours after exposure to the SIV virus.

Gilead Sciences, which has worldwide rights to PMPA, is conducting additional preclinical testing in preparation for human clinical studies to further assess the potential applications of PMPA in the treatment of HIV.

PMPA - Mechanism of Action

PMPA is a member of a new class of antiviral therapeutics known as nucleotide analogs. Nucleotide analogs are based upon the building blocks of DNA and RNA and are capable of inhibiting enzymes required for viral replication.

PMPA is known to inhibit reverse transcriptase, one of the essential enzymes used by the HIV virus in its replication cycle. Nucleotides, such as PMPA, are characterized by their ability to inhibit viral replication for long periods of time following a single dose and by their ability to be active in virally infected cells as well as in uninfected and/or resting cells, where nucleotides may form protective reservoirs of active drug.

PMPA is structurally similar to another reverse transcriptase inhibitor being developed by Gilead Sciences and known as GS 840 or bis-POM PMEA. GS 840 is in Phase I/II human studies for the potential treatment of HIV and has demonstrated anti-HIV activity against surrogate markers of the virus in human studies. GS 840 is also in Phase I/II human studies for the potential treatment of hepatitis B infection.

Gilead's most advanced products under development are VISTIDE(TM) (cidofovir intravenous) and intraocular cidofovir for the treatment of CMV retinitis. In addition to nucleotide product candidates in clinical studies for the treatment of HIV, the Company also has ongoing clinical studies for viral diseases caused by human papillomavirus, herpes simplex virus and hepatitis B virus infection.

Gilead Sciences is a leader in the discovery and development of a new class of human therapeutics based on nucleotides, the building blocks of DNA and RNA.

The Company's research and development efforts encompass three interrelated programs: small molecule antivirals, cardiovascular therapeutics and genetic code blockers for cancer and other diseases. Gilead's expertise in each of these areas has also resulted in the discovery of non-nucleotide product candidates that expand the Company's technology platforms. Gilead common stock is traded on The Nasdaq Stock Market under the symbol GILD.

Note to Editors: A PMPA fact sheet and Mechanism of Action diagram can be obtained from Lana Lauher at 415/573-4858. Members of the media may obtain a copy of the 11/17/95 Science article by calling 202/326-6440; all other interested parties may obtain copies from the reprint office at 202/326-6417.

Additional written materials and recent releases regarding Gilead Sciences are available through the Company's Fax-On-Demand Information Service by dialing 1-800-276-7318.

CONTACT: Gilead Sciences, Inc. Lana Lauher, 415/573-4858 or Edelman Worldwide Mariann Caprino, 212/704-4525

Copyright (c) 1995/PR NewsWire. Reproduced with permission. Reproduction of this article (other than one copy for personal reference) must be cleared through the Permissions Desk, PR Newswire, 810 Seventh Avenue, New York, NY 10019.
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