48-Week Data Compare Viread to Stavudine When Used as Part of Patients' First Anti-HIV Regimen; Data Presented at XIV International AIDS Conference in Barcelona

BARCELONA, Spain, Jul 8, 2002 (BUSINESS WIRE) -- Gilead Sciences, Inc. (Nasdaq:GILD) today reported 48-week results from an ongoing Phase III clinical trial (Study 903) comparing Viread(TM) (tenofovir disoproxil fumarate) in terms of efficacy and safety to stavudine (d4T) when used as part of a first-line treatment regimen in HIV patients. The data will be presented by Schlomo Staszewski, M.D., University Hospital, J.W. Goethe-Universitat, Frankfurt, Germany in the late-breaker session (presentation #LbOr17) on Friday, July 12 at the XIV International AIDS Conference in Barcelona, Spain. These are the first data from a large, controlled trial on the use of Viread in patients who have not previously received antiretroviral medications. This presentation is one of 16 Viread abstracts to be featured at the conference.

The U.S. Food and Drug Administration approved Viread for marketing in October 2001 and the European Commission granted approval in February 2002. Summary results from Study 903 were announced in a press release in May 2002.

"Data from this large study in treatment-naive patients demonstrate Viread is associated with potent anti-HIV activity and is well-tolerated," said Dr. Staszewski, a lead investigator for the study. "Importantly, analyses of measurements of laboratory markers reveal that patients in the stavudine arm of the study experienced significant increases in triglyceride and cholesterol levels compared to those in the Viread arm through 48 weeks. These are important data for clinicians to consider as they design an antiretroviral regimen for the long-term management of their patients."

"The data from this study support the use of Viread as part of a patient's first-line regimen, and should give physicians increased confidence in their ability to strategically construct effective, tolerable regimens that do not include a thymidine analogue drug such as AZT or d4T -- perhaps the next standard that we will see emerge in the treatment of HIV infection," Dr. Staszewski continued.

    Study Design
Study 903 is a three-year, randomized, double-blind, active-controlled clinical trial being conducted at 81 sites in the United States, Europe and South America. The trial was designed to compare the efficacy and safety of a treatment regimen of Viread, lamivudine (3TC) and efavirenz to a regimen of stavudine, 3TC and efavirenz in 600 antiretroviral-naive patients with HIV infection. To maintain the blinded nature of the study, patients in the Viread arm received one tablet, twice daily of stavudine placebo while patients in the stavudine arm received one tablet, once daily of Viread placebo. Treatment assignments will remain blinded to patients and their physicians through 144 weeks.

The primary efficacy endpoint of the study is the proportion of patients in each arm achieving HIV RNA suppression below 400 copies/mL at week 48. Additional efficacy endpoints include the proportion of patients in each study arm who achieve viral suppression below 50 copies/mL at week 48, as well as increases in CD4 cell count.

    Study Results
At baseline, the mean HIV RNA for the intent-to-treat (ITT) population was 4.9 log10 copies/mL and the mean CD4 cell count was 279 cells/mm3. The mean age of the study population was 36 years at the time of enrollment, with 24 percent of patients female and 64 percent Caucasian.

In the analysis of the ITT population, in which missing data are counted as failures, an identical 87 percent of patients in the Viread arm (n=299) and the stavudine arm (n=301) achieved suppression of HIV RNA below 400 copies/mL following 48 weeks of treatment (95 percent confidence interval (CI): -6 percent, +5 percent). When missing data are excluded, 95 percent of patients receiving Viread compared to 96 percent of patients receiving stavudine had reductions in HIV RNA to below 400 copies/mL (95 percent CI: -4 percent, +2 percent).

The proportion of patients achieving HIV RNA suppression below 50 copies/mL also was evaluated in the study. In the missing equals failure analysis, 82 percent of patients in the Viread arm compared to 81 percent of patients in the stavudine arm achieved this result (95 percent CI: -6 percent, +6 percent). When missing data are excluded, 90 percent of patients in the Viread arm compared to 89 percent in the stavudine arm had reductions in HIV RNA to below 50 copies/mL (95 percent CI: -4 percent, +5 percent).

Additionally, the mean reduction in HIV RNA for both treatment groups was 3.09 log10 copies/mL. At 48 weeks, combination treatment including Viread was associated with a mean increase from baseline in CD4 cells of 169 cells/mm3 and treatment including stavudine was associated with a mean increase from baseline of 167 cells/mm3.

    Evaluation of Safety Parameters
In each treatment group, therapy was generally well tolerated and the study discontinuation rate was nine percent. As a result of adverse events, one percent of patients in both the Viread arm and stavudine arm discontinued participation in the study. The incidence of grade 3/4 adverse events in the Viread-containing study arm was 19 percent compared to 17 percent in the stavudine-containing study arm. The incidence of grade 3/4 laboratory abnormalities in the Viread arm was 28 percent compared to 31 percent in the stavudine arm.

Of the laboratory markers evaluated, a statistically significant difference was seen between the two treatment arms in changes in triglycerides and cholesterol levels. Patients receiving Viread (n=242) had no mean change from baseline in triglycerides, compared to an increase of 74 mg/dL for patients in the stavudine arm (n=253; p less than 0.001). Increases in cholesterol levels for patients receiving Viread and stavudine were 25 mg/dL and 53 mg/dL, respectively (p less than 0.001). In addition, the incidence of mitochondrial-associated toxicities in the Viread-containing arm was three percent, compared to eleven percent in the stavudine-containing arm.

"The results of this study, along with data discussed in the additional abstracts to be presented this week, continue to suggest that Viread may provide a potent and safe therapeutic option for HIV patients across the spectrum of treatment stages," commented John C. Martin, Ph.D., President and Chief Executive Officer, Gilead Sciences. "We are particularly interested in the data that suggest a lower incidence of lipid abnormalities for patients treated with Viread, as compared to stavudine. We will continue to monitor both study groups for an additional two years in a blinded fashion to best evaluate how these data impact patients and the long-term success of their therapy."

    About Viread
Viread is the first nucleotide analogue reverse transcriptase inhibitor (NtRTI) approved for the treatment of HIV in the United States and Europe. It was approved in the United States in October 2001 and was approved in the European Union in February 2002. In clinical trials and expanded access programs, approximately 10,000 patients have been treated with Viread alone or in combination with other antiretroviral products for periods up to three years. 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 for use 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 is approved in Europe for use in combination with other antiretroviral agents for the treatment of HIV infection in patients who are experiencing early virological failure.

    Safety Profile
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.

    About HIV/AIDS
More than 920,000 Americans and 560,000 Europeans are infected with HIV, the virus that causes acquired immunodeficiency syndrome (AIDS). Each year, approximately 560,000 U.S. and European patients receive anti-HIV treatment regimens. Globally, it is estimated that 40 million individuals are living with HIV. Treatment with antiretroviral agents is crucial to control viral load and delay the emergence of the debilitating AIDS-defining events.

    About Gilead Sciences
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. Such risks and uncertainties include the risk that these 48-week data will not be observed through longer treatment periods and uncertainty regarding inclusion of these data in the Viread product label. 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.

    For complete prescribing information, please visit www.viread.com.
    Viread is a trademark of Gilead Sciences, Inc.
For more information on Gilead Sciences, please visit the company's web site at www.gilead.com or call the Gilead Corporate Communications Department at 1-800-GILEAD-5 or 1-650-574-3000.

CONTACT:          Gilead Sciences, Inc.
                  Susan Hubbard, 650/522-5715 (Investors)
                  Amy Flood, 44-7715-809-567 (Media)

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