Business Wire - June 29, 1999

Adefovir dipivoxil received "fast track" designation from the FDA and is expected to receive a six-month priority review for accelerated approval. Gilead intends to submit an application to market adefovir dipivoxil in the European Union later this year.

The NDA contains safety results compiled from clinical studies of more than 7,000 patients, and efficacy data from more than 1,000 patients treated with adefovir dipivoxil-containing regimens. These data suggest that therapy with adefovir dipivoxil results in antiviral activity in treatment-experienced patients who have developed resistance to commonly used antiretroviral medications.

"One of the biggest challenges physicians face today is finding anti-HIV drugs with activity against resistant viral strains," said clinical investigator John Mellors, M.D., Associate Professor of Medicine and Pathology, University of Pittsburgh. "Given the antiviral activity observed in clinical studies of adefovir dipivoxil in the presence of the most common mutation in treatment-experienced patients -- the lamivudine-induced M184V mutation -- this compound may be a new option for the growing number of patients whose viral load is no longer adequately controlled by current therapy."

Treatment-Experienced Patients Need New Treatment Options

By taking combinations of three or more potent anti-HIV drugs to block viral replication, many patients infected with HIV are living longer, healthier lives. For some, this approach can be so successful that HIV is no longer detectable in the bloodstream by standard tests. However, initial treatment success is difficult to maintain for many patients. Of the nearly 345,000 patients currently receiving anti-HIV treatment in the United States(1), an estimated 60 percent have failed their current treatment regimen(2), in part due to the development of drug resistance caused by viral mutations. In the first three months of this year alone, treatment failures contributed to an estimated 30,000 RTI switches(3) made by patients to either maintain or regain control of viral replication.

"Submitting the NDA for adefovir dipivoxil is an important milestone toward our goal of providing new therapeutic options to patients with unmet medical needs in an accelerated manner," said John C. Martin, Ph.D., President and Chief Executive Officer of Gilead Sciences. "With more than 8,300 patients enrolled in the adefovir dipivoxil expanded access program, there is evidence that patients are exhausting their therapeutic options and need access to new treatments that remain active against resistant strains of HIV."

Adefovir dipivoxil, the first anti-HIV drug from a new class of antivirals known as nucleotides, is dosed as a single daily 60 mg oral tablet taken with or without food. It is co-administered with 500 mg of the oral nutrient L-carnitine to replenish body carnitine levels that may be reduced by the administration of adefovir dipivoxil.

The NDA includes data from 17 clinical studies of adefovir dipivoxil as monotherapy or in combination with numerous approved and investigational antiretroviral therapies, including nucleoside RTIs, non-nucleoside RTIs and protease inhibitors, in treatment-naive and treatment-experienced patients. The filing is accompanied by a separate NDA for L-carnitine, which will allow Gilead to manufacture and co-package the nutrient with adefovir dipivoxil for improved patient compliance.

Safety Profile

Nephrotoxicity (or kidney dysfunction), including changes in serum creatinine and phosphate, is the most important and significant drug-related toxicity. These changes in kidney function are generally gradual in onset and can be effectively managed by routine monthly laboratory monitoring and, where indicated, by dose interruption. In addition, the most common side effects reported during clinical testing with adefovir dipivoxil for HIV have been dose-related gastrointestinal effects, including nausea and diarrhea. Elevations in liver transaminases also have been observed in some patients.

In an effort to minimize the occurrence of adverse events in clinical practice, Gilead has developed and submitted in the NDA a comprehensive Risk Management Program to reinforce the need for physicians, pharmacists and patients to adhere with recommended monthly blood monitoring and other toxicity management guidelines.

Ongoing Clinical Program

In addition to ongoing clinical trials of adefovir dipivoxil, Gilead will conduct two confirmatory Phase IV trials in the United States, Europe, Canada and Australia. These trials, one of which has begun enrolling patients and the other to begin this summer, are designed to further characterize the safety and efficacy of adefovir dipivoxil 60 mg, explore emerging HIV treatment strategies and satisfy regulatory guidelines for accelerated approval. To help meet the needs of treatment-experienced patients worldwide, Gilead recently extended its expanded access program for adefovir dipivoxil to France and Canada, and intends to begin the program in Australia and other countries of the European Union this year.

Patients and physicians who would like more information and enrollment criteria for ongoing studies of adefovir dipivoxil for HIV may call 1-800-GILEAD-5 (toll-free in the U.S.) or 1-650-522-5850 (from outside the U.S.). Information about clinical trial locations also may be found by using the Clinical Trial Locator on the Gilead Web site at www.gilead.com.

Trade Name

In Gilead's expanded access program, adefovir dipivoxil has been referred to under the trade name "PREVEON(R)." The Nomenclature Committee of the FDA has informed Gilead that it should adopt a new trade name for adefovir dipivoxil because of a conflict with the trade name of a recently approved pharmaceutical product. Gilead intends to announce an alternative United States trade name for adefovir dipivoxil at or shortly before commercial availability.

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 adefovir dipivoxil for HIV, regulatory review of these filings 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 the Gilead Annual Report on Form 10-K for the year ended December 31, 1998 on file with the U.S. Securities and Exchange Commission, copies of which are available from Gilead.

-0-

*T

(1) Scott-Levin, First Quarter 1999;

(2) ISIS, HIV in the USA, April 1999;

(3) Scott-Levin, HIV Therapy Audit, First Quarter 1999

*T

-0-

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 1-800-GILEAD-5 (1-800-445-3235)

--30--slt/sf*

CONTACTS: Gilead Sciences, Inc. Susan Hubbard, 650/522-5715 (Investors) Sheryl Meredith, 650/522-5505 (Media)
990629
BW990613

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. .