Business Wire - Friday, March 19, 1999

These data will be presented in a satellite symposium titled, "Clinical Update on Antiviral Drugs" at the 12th International Conference on Antiviral Research in Jerusalem, Israel on March 21, 1999 from 2:00 to 5:00 p.m.

"It is encouraging to see data showing comparable efficacy between the 60 mg and 120 mg doses of adefovir dipivoxil," said Clinical Investigator Joel E. Gallant, MD, MPH, Associate Professor of Medicine in the Division of Infectious Diseases at Johns Hopkins University School of Medicine. "With the improved safety profile of the 60 mg dose, adefovir may offer patients with limited treatment options a therapeutic alternative that can be used for extended treatment periods."

Monotherapy: Anti-HIV Activity in Study 420

This four-week, randomized, double-blind, placebo-controlled study was designed to determine the anti-HIV activity of PREVEON 60 mg once-daily monotherapy compared to placebo in treatment-naive, HIV-infected patients. Preliminary results demonstrate that treatment with PREVEON was associated with a mean decline from baseline in HIV RNA of -0.25 log10 at week four compared to an increase of +0.08 log10 in the placebo group (p less than 0.008) as determined by PCR assay. The difference in activity between active and placebo doses was similar in magnitude to the anti-HIV activity of PREVEON 120 mg monotherapy demonstrated in previous short-term dosing studies.

Forty-seven patients with HIV RNA greater than 5,000 copies/mL and CD4 cell counts greater than or equal to 150 cells/mm3 were randomized in a 2:1 manner to receive PREVEON 60 mg or placebo. At baseline, mean HIV RNA levels were 4.5 log10 and 4.7 log10 for the PREVEON and placebo groups, respectively. Significant anti-HIV activity for PREVEON compared to placebo was apparent after one week of treatment, continuing through the end of the four-week double-blind period.

Combination Therapy: Anti-HIV Activity in Study 417

This 48-week, double-blind, dose-comparison trial was designed to evaluate the relative safety and efficacy of the 60 mg and 120 mg doses of PREVEON in treatment-experienced, HIV-infected patients. Preliminary results demonstrate that triple drug regimens containing PREVEON 60 mg were as effective as triple drug regimens containing the 120 mg dose with regard to the proportion of patients whose HIV RNA was below the limit of quantification (less than or equal to 400 copies/mL) at week 20, the primary efficacy endpoint of the study. In the 60 mg arm, 42 percent of patients achieved plasma levels of HIV RNA below the limits of quantification compared to 33 percent of patients in the 120 mg treatment arm. The 95% Confidence Interval for the difference between the two dose arms (8.9%) is -4.3 to 22.1.

Preliminary analysis of secondary efficacy endpoints provides additional supportive data. Combination therapy including either the 60 mg or the 120 mg dose of PREVEON was associated with a mean reduction from baseline in HIV RNA of 1.2 log10 after 20 weeks. Similar changes from baseline in CD4 cell counts were observed with mean increases of 86 cells/mm3 and 76 cells/mm3 in the 60 mg and 120 mg PREVEON groups, respectively.

Improved Safety Profile

Patients receiving the 60 mg dose of PREVEON also had an approximate 30 to 50 percent reduction in the incidence of drug-related nephrotoxicity compared to those receiving the 120 mg dose. Kaplan-Meier estimates after 42 weeks of therapy show that elevations in serum creatinine of greater than or equal to 0.5 mg/dL above baseline occurred in 29 percent of patients in the 60 mg PREVEON group, compared to 42 percent in the 120 mg arm (p=0.05). Similarly, decreases in serum phosphate to less than 2.0 mg/dL occurred in 26 percent of patients in the 60 mg arm compared to 49 percent of patients in the 120 mg arm (p=0.03). This study remains double-blinded and dosing will continue through the completion of 48 weeks of therapy for enrolled patients.

Study 417 Background

Patients enrolled in the study were required to have levels of HIV RNA greater than 5,000 copies/mL and CD4 cell counts greater than or equal to 100 cells/mm3. Participants had not previously received protease inhibitors but had received prior treatment with nucleoside reverse transcriptase inhibitors.

A total of 211 patients at 22 U.S. centers were randomly assigned to receive either PREVEON 60 mg (n=107) or 120 mg (n=104) along with a combination of either nelfinavir and saquinavir or of a nucleoside reverse transcriptase inhibitor (AZT, 3TC or d4T) plus nelfinavir or saquinavir.

At baseline, mean HIV RNA levels were 4.5 log10 and 4.6 log10 in the 60 mg and 120 mg PREVEON groups, respectively. In addition, patients in both treatment groups had previously received prolonged treatment with multiple nucleoside reverse transcriptase inhibitors. Mean prior zidovudine (ZDV) usage was 90 and 96 weeks, respectively, in the 60 mg and 120 mg PREVEON arms.

PREVEON New Drug Application

In November 1998, the U.S. Food and Drug Administration granted Fast Track designation to PREVEON for the treatment of HIV-infected patients. Gilead intends to file a New Drug Application (NDA) for the accelerated approval of PREVEON 60 mg for the treatment of HIV-infected patients with clinical, immunologic or virologic progression despite prior reverse transcriptase inhibitor therapy in the second quarter of this year. In January 1999, Gilead initiated a rolling submission by filing the Chemistry, Manufacturing and Controls section of the NDA.

Gilead intends to initiate additional confirmatory studies during 1999 to better characterize the long-term efficacy and safety of PREVEON 60 mg and satisfy traditional regulatory guidelines for drug approval. Study 415 is a multinational trial planned to evaluate PREVEON 60 mg as intensification therapy when added to highly active antiretroviral treatment. In Australia and Europe, Study 432 will evaluate PREVEON 60 mg as part of a protease inhibitor-sparing treatment strategy. Study 434 is a Canadian trial designed to evaluate the anti-HIV effect of a standard triple drug regimen compared to a simplified once daily combination regimen including PREVEON.

Background on PREVEON

PREVEON is an investigational, once-daily, orally administered, reverse transcriptase inhibitor under development for the potential treatment of HIV. To date, more than 8,500 patients have been enrolled in clinical studies of PREVEON, including more than 7,000 in the Expanded Access Program. In all studies, PREVEON is co-administered with L-carnitine, a nutritional supplement.

During clinical testing, the most common side effects reported with PREVEON have been dose-related gastrointestinal effects, including nausea and loss of appetite. Nephrotoxicity, including changes in serum creatinine and phosphate, is the most important drug-related toxicity. These changes are generally gradual in onset, asymptomatic, detectable by routine monitoring and resolvable upon dose reduction or withdrawal. Elevations in liver transaminases have been observed in some patients.

Gilead Sciences

Gilead Sciences is an independent biopharmaceutical company that seeks to provide accelerated treatment solutions for patients and the people who care for them. The company discovers, develops and commercializes proprietary therapeutics for important viral diseases, including a currently marketed product, VISTIDE(R) (cidofovir injection), for the treatment of CMV retinitis, a sight-threatening viral infection in patients with AIDS. In addition, the company is developing products to treat diseases caused by HIV, hepatitis B virus and influenza virus.

This press release contains forward-looking statements, within the meaning of the Private Securities Litigation Reform Act of 1995, concerning the timing and nature of potential registration filings for PREVEON and presentation of clinical data at scientific conferences. Such statements are subject to certain risks and uncertainties, particularly those inherent in the process of discovering, developing and commercializing drugs that are safe and effective as human therapeutics. Actual results could differ materially from those projected in this release. The reader is cautioned not to rely on these forward-looking statements. These and other risks are described in detail in Gilead's Annual Report on Form 10-K for the year ended December 31, 1997 on file with the U.S. Securities and Exchange Commission, copies of which are available from Gilead.

Note to Editors: PREVEON and VISTIDE are registered trademarks of Gilead Sciences, Inc.

To receive more information, please visit the Gilead Web site at www.gilead.com or call Corporate Communications at 800/GILEAD-5 (800/445-3235)

CONTACT: Gilead Sciences, Inc. Susan Hubbard, 650/522-5715 (Investors) Sheryl Meredith, 650/522-5505 (Media)
990319
BW990307

Copyright © 1999 - Business Wire. All rights reserved. Reproduced with permission. Reproduction of this article (other than one copy for personal reference) must be cleared through the Business Wire, Permissions Desk, Business Wire, 1185 Avenue of the Americas, 3rd Floor, New York, NY 10036; Tel: (212) 575-8822; FAX: (212) 575-1854. http://www.businesswire.com.

AEGiS is a 501(c)3, not-for-profit, tax-exempt, educational corporation. AEGiS is made possible through unrestricted funding from Broadway Cares/Equity Fights AIDS, Elton John AIDS Foundation, the National Library of Medicine, Pacific Life Foundation and donations from users like you.

Always watch for outdated information. This article first appeared in 1999. This material is designed to support, not replace, the relationship that exists between you and your doctor.

AEGiS presents published material, reprinted with permission and neither endorses nor opposes any material. All information contained on this website, including information relating to health conditions, products, and treatments, is for informational purposes only. It is often presented in summary or aggregate form. It is not meant to be a substitute for the advice provided by your own physician or other medical professionals. Always discuss treatment options with a doctor who specializes in treating HIV.

Copyright ©1980, 1999. AEGiS. All materials appearing on AEGiS are protected by copyright as a collective work or compilation under U.S. copyright and other laws and are the property of AEGiS, or the party credited as the provider of the content. .