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  (editorial note: you can read information, study results, and safety information about Tenofovir at the NATAP website www.natap.org by using the search engine for Tenofovir)
Foster City, CA, May 21, 2002 - Gilead Sciences, Inc. (Nasdaq: GILD) today announced the initiation of a collaborative Phase I clinical trial to evaluate the safety and acceptability of the experimental topical gel formulation of the antiviral tenofovir as a potential prevention method for vaginal transmission of the human immunodeficiency virus (HIV). Tenofovir is the active ingredient in Gileads oral antiretroviral drug Vireado (tenofovir disoproxil fumarate), which was approved for marketing by the U.S. Food and Drug Administration (FDA) in October 2001 and by the European Commission in February 2002 as an anti- HIV treatment.
Phase I study (HPTN 050) is sponsored by the Division of AIDS of the National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), and is being conducted by the HIV Prevention Trials Network under the auspices of Family Health International.
Recent statistics estimate that worldwide nearly 40 million adults and children were living with HIV/AIDS at the end of 2000, and that each day 15,000 new HIV infections occur. Because the majority of HIV is transmitted through heterosexual contact, public health experts have identified the need for new ways to prevent the sexual transmission of HIV. While condom use has been shown to prevent HIV transmission, public health experts point out that women often are unable to negotiate the proper use of condoms by their male partners.
"Tenofovir topical gel is a very exciting investigational microbicide because it is the first one that contains an antiretroviral agent,ls said Lisa A. Maslankowski, MD, Principal Investigator, University of Pennsylvania and Co-Chair of the Phase I clinical trial. Unlike other microbicides, when HIV comes in contact with an uninfected T-cell, tenofovir is already activated to prevent the HIV virus from replicating. If HIV is unable to reproduce, it is unlikely to survive long enough to cause systemic infection.
"Even if the use of a topical microbicide, such as tenofovir, could prevent half of the new HIV infections estimated to occur, that would potentially mean that as many as 7,500 people each and every day could be spared from contracting this terrible disease", continued Dr. Maslankowski.
Another compelling characteristic of tenofovir is its potent activity against strains of HIV that have become resistant to other anti-HIV drugs,lV explained Dr. Maslankowski. With the increasing incidence of patients who become infected with multidrug-resistant HIV, it is important that a topical microbicide remain active against a variety of HIV mutations. In vitro data show that tenofovir is a potent inhibitor of many drug-resistant strains of HIV.
As a member of the novel class of antivirals called nucleotide analogues, tenofovir is characterized by its ability to enter and inhibit viral repli cation in infected and uninfected or resting cells, where it may form protective reservoirs of active drug.
Tenofovir also has a long intracellular half-life, which is an important characteristic for drugs designed to treat chronic viral infections.
About the Phase I Tenofovir Microbicide Study
This Phase I study (HPTN 050) will enroll up to 96 women and their male sexual partners (as relevant) at three sites in Philadelphia, PA, New York, NY and Providence, RI. During the study, tenofovir topical gel will be applied intravaginally for 14 consecutive days with a 21-day follow-up period. The dosage and frequency of treatment will be escalated to determine the optimal clinical dose. The antiviral efficacy of tenofovir topical gel will not be evaluated in this Phase I study.
At the conclusion of the study, patients will be evaluated for signs of the effects of daily use of tenofovir topical gel including symptoms of irritation or other systemic side effects. Secondary endpoints include degree of acceptance of the treatment by study participants and their sexual partners. A subgroup of women will be tested to see if the active ingredient in tenofovir gel is absorbed into the bloodstream.
This study protocol went through a rigorous peer-review process by NIH committees and clinical researchers before being approved for conduct by the HIV Prevention Trials Network, said Kenneth Mayer, MD, Principal Investigator, Miriam Hospital and Brown University, Providence, RI and Co-Chair of the Phase I clinical trial. The feedback we received indicates that the research community is very enthusiastic about the potential development of tenofovir as a topical microbicide.
Early Animal Data
Animal studies in monkeys have demonstrated the potential of tenofovir to prevent transmission of simian immunodeficiency virus (SIV). Intravaginal application of tenofovir gel, beginning 24 hours before and continuing for 48 hours after intravaginal inoculation with SIV, resulted in 100 percent protection in four female rhesus macaques, compared with evidence of infection in both of the two animals receiving placebo gel. In a separate four-week study of macaques, daily subcutaneous injections of tenofovir, beginning either 48 hours before or up to 24 hours after exposure to SIV, resulted in 100 percent protection against acute SIV infection in 25 treated animals. In comparison, all 10 animals receiving placebo 48 hours prior to inoculation became infected. SIV infection in primates is a commonly used evaluation model for HIV in humans.
We are pleased to be working with the NIAID to explore additional applications of this important antiviral beyond the treatment setting. As a topical microbicide gel, tenofovir may be able to help prevent the thousands of new HIV infections that occur each year, and consequently help slow the growing magnitude of the worldwide AIDS epidemic,ll said John C. Martin, PhD, President and Chief Executive Officer of Gilead. iiFrom our controlled clinical trials of the drug's oral formulation, Viread, we know that the unique molecular properties of tenofovir can result in a valuable anti-HIV treatment. We will continue to work with government, the advocacy community and international health organizations to explore additional uses of tenofovir to potentially extend its therapeutic benefits to a greater variety of patient populations in need.
About Viread
Tenofovir is the active ingredient in Gileads oral antiretroviral drug Viread, which is the first nucleotide analogue reverse transcriptase inhibitor (NtRTI) approved for the treatment of HIV in the United States and Europe. The drug works by blocking reverse transcriptase, an enzyme involved in the replication of HIV. The approved dose of Viread for the treatment of HIV infection is 300 mg once daily taken orally with a meal.
In the United States, Viread is indicated in combination with other antiretroviral agents for the treatment of HIV-1 infection. This indication is based on analyses of plasma HIV-1 RNA levels and CD4 cell counts in a controlled study of Viread of 24 weeks duration and in a controlled, dose ranging study of Viread of 48 weeks duration. Both studies were conducted in treatment-experienced adults with evidence of HIV-1 viral replication despite ongoing antiretroviral therapy. Studies in antiretroviral-naive patients are ongoing; consequently, the risk-benefit ratio for this population has yet to be determined.
Viread Safety Profile
Approximately 10,000 patients have been treated with Viread alone or in combination with other antiretroviral products for periods up to three years in clinical trials and expanded access programs. Assessment of adverse reactions is based on two studies (902 and 907) in which 653 treatment-experienced patients received treatment with Viread 300 mg (n=443) or placebo (n=210) for 24 weeks followed by extended treatment with the drug. Adverse event rates in the Viread group were similar to those in the placebo -treated patients.
The most common adverse events in patients receiving Viread were mild to moderate gastrointestinal events, such as nausea, diarrhea, vomiting and flatulence. Laboratory abnormalities observed in clinical studies occurred with similar frequency in the Viread and placebo-treated groups. Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogues alone or in combination with other antiretrovirals.
Gilead Sciences, Inc.
Gilead Sciences is a biopharmaceutical company that discovers, develops and commercializes therapeutics to advance the care of patients suffering from life-threatening diseases worldwide. The company has five marketed products and focuses its research and clinical programs on anti-infectives, including antivirals, antifungals and antibacterials. Headquartered in Foster City, CA, Gilead has operations in the United States, Europe and Australia.
This press release includes forward-looking statements, within the meaning of the Private Securities Litigation Reform Act of 1995, that are subject to risks, uncertainties and other factors that could cause actual results to differ materially from those referred to in the forward-looking statements. For example, in vitro and animal data for tenofovir referred to in this press release cannot predict with certainty clinical success in humans. Accordingly, there is a risk that these data will not be observed in human studies. The reader is cautioned not to rely on these forward-looking statements. These and other risks are described in detail in the Gilead Annual Report on Form 10-K for the year ended December 31, 2001 and in Gilead's Quarterly Reports on Form 10-Q, all of which are on file with the U.S. Securities and Exchange Commission. All forward-looking statements are based on information currently available to Gilead and Gilead assumes no obligation to update any such forward-looking statements.
Note to Editors: The following are principal investigators in the tenofovir gel microbicide study:
Wafaa El-Sadr, MD
Principal Investigator
Harlem Hospital
New York, NY
Lisa Maslankowski, MD
Principal Investigator
University of Pennsylvania
Philadelphia, PA
Kenneth Mayer, MD
Principal Investigator
Miriam Hospital and
Brown University
Providence, RI
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