Gilead Sciences' Viread Suppresses HIV Viral Load Through 48 Weeks in Phase III Clinical Trial

SEATTLE, Feb 25, 2002 (BUSINESS WIRE) --

- Additional Long-Term Safety Data Presented at 9th Conference on Retroviruses and Opportunistic Infections -

Gilead Sciences (Nasdaq:GILD) today announced 48-week efficacy and safety data from a Phase III clinical trial (Study 907) of its novel one-tablet, once-daily antiretroviral agent Viread(TM) (tenofovir disoproxil fumarate) for the treatment of HIV infection. Study results demonstrate that highly treatment-experienced HIV-infected patients who received Viread 300 mg in addition to their existing antiretroviral regimen achieved a significant HIV RNA reduction, durable through 48 weeks. Viread was approved for the treatment of HIV infection in the United States in October 2001 and was approved earlier this month in Europe.

The data are scheduled for presentation (#413-W) at the 9th Conference on Retroviruses and Opportunistic Infections in Seattle by Kathleen Squires, MD, Associate Professor of Medicine, Keck School of Medicine, University of Southern California.

"These results clearly demonstrate that Viread can produce a durable antiviral response in patients who have developed resistance to available drugs, offering new hope for successful long-term treatment," said Dr. Squires. "Viral resistance is one of the most serious challenges facing long-term HIV treatment today, and Viread's favorable resistance profile, combined with its proven efficacy and safety profile, represent a major step forward."

    About Study 907
Study 907 was a 48-week Phase III, double-blinded, placebo-controlled clinical trial of Viread 300 mg added to a stable background regimen of antiretroviral agents in 550 treatment-experienced HIV patients in North America, Europe and Australia. To be eligible for the study, patients had to have an HIV RNA level of 400 to 10,000 copies/mL (a measure of the amount of HIV in their blood) and have received stable antiretroviral therapy for at least eight weeks prior to entering the study. At baseline, patients had a mean HIV RNA level of 3.36 log(10) copies/mL, a mean CD4 cell count of 427 cells/mm(3) and had received a mean of 5.4 years of prior antiretroviral therapy. Genotypic analysis of resistance mutations at baseline revealed a high prevalence of existing antiretroviral resistance, with 94 percent of patients exhibiting resistance to nucleoside analogue reverse transcriptase inhibitors (NRTIs), 58 percent to protease inhibitors (PIs) and 48 percent to non-nucleoside reverse transcriptase inhibitors (NNRTIs).

Upon entry into the study, patients were randomized (2:1) to receive Viread or placebo in addition to their existing antiretroviral therapy. After 24 weeks of blinded, placebo-controlled dosing, all patients were switched to receive open-label Viread for the remainder of the 48-week study period. The 24-week results met the study's primary efficacy endpoint of reduction in viral load. At 48 weeks, study results demonstrated that patients who received Viread 300 mg in addition to their existing antiretroviral regimen (n=368) achieved a significant mean HIV RNA reduction (DAVG48) of 0.57 log(10) copies/mL, similar to that observed at week 24. In addition, 48-week results revealed that 41 percent of patients achieved a reduction in HIV RNA to less than 400 copies/mL, also consistent with 24 week data. The mean average increase in CD4 cells was 13 cells/mm(3). The safety profile of Viread was similar to that observed during the 24 week placebo-controlled portion of the trial, during which the safety of Viread was similar to placebo.

    Study 907 Virology Analysis
Results of a virology substudy of 274 patients randomly selected from Study 907 also will be presented at the conference (#414-W) by Michael Miller, Ph.D., Director, Clinical Virology, Gilead Sciences. HIV samples were genotyped and phenotyped at baseline, week 24 and week 48. At week 48, genotypic results were obtained for 145/274 patients (53 percent). At 48 weeks, 58 patients (21 percent) developed resistance to one or more NRTI. Of those, 47 patients had the common zidovudine (AZT)/thymidine analogue mutations (TAMs). Mutation development during the open-label period was similar to placebo during the first 24 weeks (22 percent), suggesting that most mutations resulted from background therapy and not Viread. As a group, patients who developed the NRTI mutations showed continued viral load suppression (HIV RNA mean DAVG48 of -0.56 log(10) copies/mL). By week 48, the K65R mutation, associated with reduced susceptibility to tenofovir, developed in a total of eight patients (three percent). These patients demonstrated a wide range of virologic responses, with three patients maintaining viral load suppression of greater than 0.6 log(10) copies/mL from baseline.

    Additional Data
The resistance profile of Viread will be further characterized in two oral presentations on Tuesday. The first (#43), given by Dr. Miller, will highlight an integrated resistance analysis of Gilead's two pivotal Viread studies. The second presentation (#44) will discuss the tenofovir crystal structure and how it helps define the compound's favorable resistance profile. This presentation will be given by Steven Tuske, Ph.D., Rutgers University.

Data from the Viread Expanded Access Program in the United States and France will be described in a poster presentation (#415-W) by Steven Follansbee, MD, Kaiser Permanente Medical Center, San Francisco, CA. Safety and efficacy analyses up to 30 weeks were available from 1,360 U.S. patients and up to 16 weeks in 813 French patients. Data from these highly treatment-experienced patients were consistent with safety and efficacy results from controlled clinical trials of Viread.

    New Prodrug of Tenofovir
In a separate presentation (#384-T), William Lee, Ph.D., Senior Vice President, Research and Product Development, Gilead Sciences described preclinical data from a new oral prodrug of tenofovir (GS7340) demonstrating the ability of this agent to remain stable in plasma and selectively target lymphatic tissue. Tenofovir is the parent compound of Viread, or tenofovir disoproxil fumarate. Gilead plans to initiate Phase I testing of GS7340 in the coming months.

"The breadth of data presented at the Retrovirus conference underscore Gilead's commitment to the fight against HIV," said John C. Martin, Ph.D., President and CEO, Gilead Sciences. "Long-term data from our Phase III clinical trial confirm the potency, safety and resistance profile of Viread observed in earlier clinical trials, and will help physicians as they evaluate the best treatment options for their patients."

    About Viread
Viread 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.

    HIV Resistance Profile
Resistance to Viread occurs in approximately three percent of patients and is slow to develop. Viread selects for the K65R mutation in HIV reverse transcriptase in vitro, and viruses expressing this mutation show a 3- to 4-fold reduced susceptibility to the drug. Zalcitabine, didanosine and abacavir can also select for this mutation. In clinical trials, three percent of patients developed the K65R mutation, which did not always result in treatment failure. The clinical significance of the K65R mutation for patients treated with Viread or other antiretroviral agents is not fully known at this time.

    Safety Profile
More than 1,000 patients have been treated with Viread alone or in combination with other antiretroviral products for a period of 28 days to 143 weeks in Phase I, II and III clinical trials and in a compassionate access study (908). 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. In this analysis, 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.

    Ongoing Clinical Studies
Gilead is conducting Study 903 to further evaluate Viread in treatment-naive patients with HIV infection. This 96-week trial is designed to compare a treatment regimen of Viread, lamivudine (3TC) and efavirenz to a treatment regimen of stavudine (d4T), lamivudine (3TC) and efavirenz in a blinded fashion in patients in the United States, Europe and South America who have not previously received antiretroviral treatment. Enrollment in Study 903 was completed in January 2001 with 601 patients. In addition, Gilead has initiated a program to evaluate Viread in treatment-experienced pediatric patients.

    About HIV/AIDS
More than 900,000 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. Treatment with antiretroviral agents is crucial to control viral load and delay the emergence of the debilitating AIDS-defining events. Over years of treatment with existing agents, however, multiple factors can lead to the development of viral mutations that render patients' HIV resistant to currently available medications.

    About Gilead
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, including the risk that the safety and efficacy data observed in the studies described in this press release may not continue to be observed in broader patient groups or through longer periods of treatment. 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 Dec. 31, 2000 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.

    Viread is a trademark of Gilead Sciences, Inc.
For full prescribing information on Viread, please call 1-800-GILEAD-5 (1-800-445-3235) or visit www.viread.com.

Note: In "log(10)" the 10 is subscript; in cells/mm(3), the 3 is superscript.

CONTACT:          Gilead Sciences
                  Susan Hubbard, 650/522-5715 (Investors)
                  Amy Flood, 650/522-5643 (Media)
                  http://www.gilead.com

URL:              http://www.businesswire.com
Today's News On The Net - Business Wire's full file on the Internet
with Hyperlinks to your home page.
Copyright (C) 2002 Business Wire.  All rights reserved.