Gilead Sciences Announces Promising Interim Results from Pivotal Study of VISTIDE in Patients with Relapsing CMV Retinitis.

FOSTER CITY, Calif.--(HealthWire)--Sept. 18, 1995--Gilead Sciences, Inc. (Nasdaq: GILD) announced today the presentation of interim data from a randomized, controlled pivotal study indicating that VISTIDE(TM) (cidofovir intravenous) delayed the time to progression of retinitis in patients with relapsing CMV retinitis, when compared to historical controls. Prior to receiving VISTIDE, these patients had experienced disease progressions despite extensive treatment with approved CMV therapies. Untreated, CMV retinitis progresses rapidly, impairs a patient's vision over time and ultimately may lead to blindness.

This interim analysis included data from the first 60 of the 126 patients enrolled to date in the multicenter, dose-comparison study. These data will be presented today at the 35th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) in San Francisco by clinical investigator Jacob Lalezari, M.D., co-director of HIV Clinical Research at the Mt. Zion Medical Center, University of California -- San Francisco.

"The results now from two clinical studies, one presented today in relapsing patients and previously in untreated CMV retinitis, demonstrate that cidofovir has a place in the management of this dreaded complication of AIDS," Dr. Lalezari said. "The data today clearly indicate that cidofovir provides an important alternative for patients with AIDS and CMV retinitis who have failed standard therapies."

Study Design

Patients with relapsing CMV retinitis were randomized to one of two VISTIDE maintenance treatment regimens. Both patient groups received initial VISTIDE induction treatment (5 mg/kg) via intravenous infusion once per week for the first two weeks of therapy, followed by one of two maintenance doses given once every other week (5 or 3 mg/kg).

Interim Analysis -- Data Summary

Patient baseline characteristics were comparable between both treatment groups, with a median CD4 count of 5 cells/mm(3). All patients in the study had previously progressed despite a median of four courses of other CMV systemic treatments and had entered this study a median of 448 days after diagnosis of CMV retinitis. Twenty percent of enrolled patients had failed local therapies, administered directly into the eye.

Data from this study indicated that VISTIDE treatment resulted in median time to progression of 115 days in the higher dose group (5 mg/kg) and median time to progression of 49 days in the lower dose group (3 mg/kg). Time to progression was measured through the use of bilateral, full-field retinal photographs evaluated by an ophthalmologist unaware of the patient's treatment assignment. At the time of dosing, patients received oral probenecid and saline hydration to minimize the potential for nephrotoxicity.

Dr. Lalezari also reported that these preliminary data suggest that VISTIDE is associated with a manageable side effect profile. Grade III/IV side effects, as defined by the study protocol, which were classified as possibly or probably related to treatment, included asymptomatic proteinuria (18%) and creatinine increases to greater than or equal to 2 mg/dL (7%) and reversible probenecid reactions (5%). Probenecid reactions described as mild to moderate, consisting of constitutional symptoms, were also observed (48%). Survival rates in the two groups were similar and consistent with historical controls.

VISTIDE Treatment IND

VISTIDE, while still an investigational drug and not yet approved for marketing by the U.S. Food and Drug Administration (FDA), is available under a Treatment IND expanded access program for patients with relapsing CMV retinitis, who have progressed despite treatment with, or who are intolerant to, an approved CMV retinitis therapy. The following toll-free information service is available for physicians, health care professionals and patients interested in obtaining information or enrolling in the Treatment IND Program: 1-800-GILEAD 5 (445-3235).

The rationale for making VISTIDE available through a Treatment IND Program is based in part on promising results from a Phase II/III randomized, controlled study of VISTIDE in patients with AIDS and previously untreated peripheral CMV retinitis. These data were first presented in January 1995 at the Second National Conference on Human Retroviruses and Related Infections. They will be presented again today in summary form at the 35th ICAAC by Dr. Lalezari, who will report a median time to progression of 120 days in the VISTIDE treated patients (5 mg/kg) versus 22 days in initially untreated patients (p=0.000005).

Gilead Sciences anticipates filing in the next several weeks a New Drug Application (NDA) with the FDA seeking approval to market VISTIDE in the United States, followed by equivalent regulatory submissions in Europe.

CMV is the most common viral opportunistic infection in patients with AIDS, with approximately 95% of patients being infected. CMV can infect several sites in the body, including the retina, gastrointestinal tract, lungs, liver and central nervous system. When CMV invades the retina, lesions form on the light-sensitive layer of cells at the back of the eye that transmits images to the brain. As these CMV lesions progress, the patient's vision deteriorates over time. Retinitis is the most frequent manifestation of CMV infection in patients with AIDS, occurring in approximately 15% to 40% of these patients.

Gilead's most advanced products under development are for CMV retinitis, which include VISTIDE and intravitreous cidofovir, the Company has multiple product candidates in clinical studies for viral diseases caused by human immunodeficiency virus (HIV), human papillomavirus, herpes simplex virus and hepatitis B virus infection.

Gilead Sciences is a leader in the discovery and development of a new class of human therapeutics based on nucleotides, the building blocks of DNA and RNA. The Company's research and development efforts encompass three interrelated programs: small molecule antivirals, cardiovascular therapeutics and genetic code blockers for cancer and other diseases. Gilead's expertise in each of these areas has also resulted in the discovery of non-nucleotide product candidates that expand the Company's technology platforms. Gilead common stock is traded on The Nasdaq Stock Market under the symbol GILD.

CONTACT: Gilead Sciences Inc.

Lana Lauher, 415/573-4858