September 23, 1998
Gilead Sciences Provides Update on PREVEON® Clinical Program for the Treatment of HIV
PREVEON Profile to be Highlighted in Five Oral Presentations at ICAAC Conference
Foster City, CA -- September 23, 1998
Gilead Sciences, Inc. (Nasdaq: GILD) announced today the completion of enrollment in three clinical studies of PREVEON (adefovir dipivoxil) and the conclusion of a fourth study. These studies (GS 411, GS 417 and GS 420 and CPCRA 039, respectively) were designed to assess the safety and efficacy of 120 mg and 60 mg doses of PREVEON, an experimental, once-a-day oral medication for the treatment of HIV. Background information on the design of each of these studies follows at the end of this press release.
Data from these studies will be collected and analyzed over the next several months. This information, in addition to data from other clinical trials of PREVEON including pivotal Study GS 408, are anticipated to form the basis of regulatory filings for marketing clearance of PREVEON in the United States and the European Union. Gilead is currently in discussions with the U.S. Food and Drug Administration regarding the content and timing of such an application.
PREVEON Profiled in Five Oral Presentations at ICAAC
Data from other studies of PREVEON will be presented in five oral presentations at the 38th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC), which will be held September 24 - 27 in San Diego, California. These presentations will highlight safety and efficacy data from late-stage clinical trials of PREVEON. These data demonstrate that PREVEON has durable anti-HIV activity in treatment-experienced patients, including those infected with strains of HIV resistant to most currently approved therapies.
These data will include findings from Study GS 408 demonstrating that at 24 and 48 weeks, PREVEON as part of combination regimens was associated with sustained decreases in levels of HIV RNA (-0.4 log10 median decrease in the PREVEON group versus no change in placebo). In addition, data from this study demonstrate that treatment with PREVEON was associated with a median reduction in HIV RNA that ranged from -0.51 log10 to -0.94 log10 in patients infected with strains of HIV known to have developed resistance to 3TC (lamivudine) and AZT (zidovudine).
Data from a 20-week interim analysis of Study GS 411 also will be presented at the Conference. Data from this study, which enrolled treatment naïve patients, suggest that once-daily treatment with PREVEON, when combined with the protease inhibitor indinavir plus either 3TC, AZT or d4T, reduced HIV RNA below the limits of detection in approximately 80 percent of patients, a finding similar to that seen in a control group receiving a standard of care regimen (indinavir, AZT and 3TC).
Another conference presentation includes data from five patients enrolled in the PREVEON expanded access program (Study GS 423). These data suggest that treatment with PREVEON, abacavir and efavirenz, a regimen that does not contain a protease inhibitor, resulted in viral load reductions in patients who have failed treatment with other antiretrovirals. An additional presentation at the Conference will include data from an interim analysis of Study GS 418, an early-stage (Phase I) trial designed to assess the pharmacokinetics and safety of PREVEON in children infected with HIV.
Side effects observed in clinical studies to date include changes in markers of renal function, dose-related gastrointestinal effects, including nausea, vomiting and loss of appetite, and increases in liver transaminases and weight loss. The renal abnormalities, including increases in serum creatinine, have been observed primarily in patients who have received PREVEON for more than 24 weeks and generally have been reversible with dose modification and/or discontinuation. In all studies, PREVEON is co-administered with L-carnitine, a nutritional supplement.
To date, more than 6,000 patients have enrolled in clinical trials of PREVEON in North America, Europe and Australia. This includes more than 4,800 patients who have received PREVEON through the Gilead expanded access program in the United States for patients with limited treatment options.
Patients and physicians who would like more information and enrollment criteria for ongoing studies of PREVEON may call the AIDS Clinical Trials Information System (ACTIS) at 1-800-TRIALS-A or Gilead Sciences Medical Information at 1-800-GILEAD-5 (1-800-445-3235).
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® (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. Gilead common stock is traded on The Nasdaq Stock Market under the symbol GILD.
Copies of the scientific abstracts presented at the ICAAC conference are available upon request by calling the Gilead Corporate Communications Department at 1-800-GILEAD-5 (1-800-445-3235).
PREVEON and VISTIDE are registered trademarks of Gilead Sciences, Inc.
Background on Clinical Studies of PREVEON
Study GS 408 - This 48 week Phase II/III study enrolled a total of 442 patients infected with HIV who had HIV RNA >2,500 copies/mL and a CD4 count 3 200 cells/mm3. In the study, patients were randomly assigned to receive treatment with either PREVEON (120 mg once per day) or placebo in addition to any approved anti-HIV treatment regimen the patient was receiving at the time of enrollment, provided that the patient had been on a stable regimen for at least eight weeks. Enrollment in this study was completed in May 1997.
Study GS 411 - This 48 week Phase II/III study enrolled a total of 224 treatment-naïve patients who had not received prior treatment with anti-HIV agents and who had a CD4 cell count 3 100 cells/mm3 and HIV RNA 35,000 copies/mL. Patients assigned to one of the four PREVEON-containing regimens received treatment with PREVEON (120 mg once per day), a protease inhibitor (indinavir) and one or two of the following reverse transcriptase inhibitors: zidovudine (ZDV), lamivudine (3TC) or stavudine (d4T). Patients in the control group received treatment with a standard-of-care triple combination regimen of ZDV, 3TC and indinavir. Enrollment in this study was completed in September 1998.
Study GS 417 - This Phase II/III study enrolled a total of 214 treatment-experienced patients not previously treated with a protease inhibitor and who had CD4 cell counts 3100 cells/mm3 and HIV RNA 35,000 copies/mL. Patients enrolled in this trial were randomized to receive either 120 mg or 60 mg of PREVEON once daily as a part of triple drug combination regimens including one or two protease inhibitors (nelfinavir or saquinavir) and/or a nucleoside reverse transcriptase inhibitor. Enrollment in this study was completed in September 1998.
Study GS 418 - This Phase I/II study has enrolled a total of 25 HIV infected children who received treatment with one of two dose levels of PREVEON (1.5 or 3.0 mg/kg) in combination with another reverse transcriptase inhibitor and the protease inhibitor nelfinavir. Enrollment in this study is ongoing.
Study GS 420 - This Phase II study enrolled a total of 47 treatment-naïve patients who had CD4 cell counts 3150 cells/mm3 and HIV RNA >5,000 copies/mL. Patients were randomized to receive either 60 mg of PREVEON once daily monotherapy or placebo for four weeks. Enrollment in this study was completed in September 1998.
Study GS 423 (Expanded Access) - This U.S. study is designed to provide PREVEON free of charge to patients with limited options who have failed treatment with currently approved regimens. Patients enrolled in the program are randomized to receive either 120 mg or 60 mg of PREVEON once daily as part of a combination regimen. After 16 weeks, patients receiving 120 mg have their dose reduced to 60 mg. The program has no CD4 or HIV RNA level requirements. To date, more than 4,800 patients have enrolled in this ongoing program.
Study CPCRA 039 - This Phase III study is being conducted by the National Institutes of Health's National Institute of Allergy and Infectious Diseases (NIAID). The placebo-controlled study was designed to assess the safety and efficacy of PREVEON (120 mg once per day) in prolonging survival in HIV infected individuals with a CD4 cell count of £100 cells/mm3 or a lifetime nadir of £50 cells/mm3. The NIAID Data and Safety Monitoring Board recently recommended that this trial be terminated early because enrollment and HIV event rates were lower than anticipated at the time the study was designed. It was estimated that due to the impact of new antiretroviral therapies on survival and disease progression, the enrollment would need to be increased from 2,200 patients to as many as 4,000 patients to adequately study the primary endpoint of survival. The study was not designed to detect differences in viral load as patients were allowed to change antiretrovirals at any time before or during the study, there were no minimum viral load requirements at study entry, and 26% percent of patients had viral load below the limit of detection at study entry. Changes in viral load between the two study arms were not significantly different. The study has yielded important placebo-controlled safety information about the use of PREVEON in patients with advanced HIV disease and was not closed to enrollment because of safety concerns. A total of 505 patients were enrolled in the study with a median follow-up of 11 months. Drug discontinuation rates over the course of the study were 38% in patients receiving PREVEON compared with 32% in patients receiving placebo. The cumulative incidence of proximal renal tubular dysfunction was 22% at 12 months in patients receiving PREVEON. Patients enrolled in the study will have the option to continue or initiate PREVEON therapy through Gilead's expanded access program.