April 28, 1998
Gilead Announces Adefovir Dipivoxil Reduces Hepatitis B Levels by More than 99 Percent in Chronically Infected Patients
Data from Phase II Clinical Study To Be Presented At Scientific Conference This Week
Foster City, CA -- April 28, 1998
Gilead Sciences, Inc. (NASDAQ:GILD) announced today that treatment with adefovir dipivoxil for 12 weeks significantly reduced blood levels of hepatitis B virus (HBV) DNA to an undetectable level in the majority of patients. When quantified with a more sensitive assay, the median HBV DNA decrease was 99.99 percent (greater than or equal to 4 log10).
These preliminary data, from the first of three dose cohorts in the Phase II program, demonstrate that adefovir dipivoxil (30 mg), given orally once per day, significantly reduced HBV DNA compared to placebo and was well tolerated. Based on these data, Gilead is designing a program of Phase III studies that will further define the potential role of adefovir dipivoxil in the treatment of chronic HBV infection.
These data will be presented Friday, April 10 at the 11th International Conference on Antiviral Research (ICAR) in a late breaker session by clinical investigator Lennox Jeffers, M.D., Professor of Medicine at the University of Miami, Florida. The conference will be held in San Diego, California, April 5-10, and a summary of these data was made available to conference participants upon on-site registration.
"Chronic hepatitis B virus infection is an enormous global medical problem," Dr. Jeffers said. "The potent 4 log10 reduction in serum HBV DNA seen with three months of adefovir dipivoxil therapy justifies rapid movement of this program to Phase III studies."
Adefovir Dipivoxil Reduces HBV DNA by 99.99 Percent
Data from the randomized, double-blind, placebo-controlled Phase II study demonstrate that treatment with adefovir dipivoxil (30 mg once per day for 12 weeks) reduced the amount of HBV DNA to undetectable levels in the majority of patients with an overall median decrease of 99.7 percent (greater than or equal to 2.5 log10) using a branched chain DNA (bDNA) assay to quantify viral load. This was a statistically significant reduction compared with HBV DNA levels in patients receiving placebo, who had a median decrease of 0.2 log10 (p < 0.001). In patients with HBV DNA below the limit of detection by bDNA, a more sensitive PCR assay was used to more precisely assess antiviral activity. Results of PCR testing demonstrated that treatment with adefovir dipivoxil resulted in a median decrease of 99.99 percent (greater than or equal to 4 log10).
In addition, some of the patients had evidence of seroconversion. Three of the 15 patients (20 percent) treated with adefovir dipivoxil lost HBe antigen, and two of the three developed HBe antibody. None of the patients on placebo seroconverted based on either marker (0 of 14). Seroconversion refers to improvements in markers of hepatitis B infection, including disappearance of HBe antigen (a marker of replicating virus) and appearance of HBe antibody (a marker of immune response against the virus).
Treatment with adefovir dipivoxil was well tolerated, and there were no significant differences in reported adverse events between the placebo and treatment groups. Elevations in liver transaminases and CK (creatine kinase), a laboratory marker of muscle metabolism that can be related to exercise or strenuous activity, were observed during the study.
This study enrolled adults in the United States, Canada, the United Kingdom and Australia, who had been chronically infected with hepatitis B virus who had elevated levels of liver enzyme markers (AST/ALT) and were HBe antigen-positive and HBe antibody-negative at baseline.
In addition to the 30 mg group, additional patients were randomly assigned to 5 mg or 60 mg dose groups as part of the Phase II study; data collection and analysis of these two additional cohorts are still ongoing.
Global Need for HBV Treatment
Chronic hepatitis B virus is a major global health problem. More than 300 million people worldwide are chronically infected with hepatitis B virus, and more than 5 million people are estimated to be infected in the United States and Europe. Chronic HBV infection can lead to severe complications, including cirrhosis, liver failure, liver cancer and even death.
Adefovir dipivoxil is also the active ingredient in PREVEON®;, which is being studied in multiple, late-stage clinical trials at different dose levels (120 mg and 60 mg once per day) for the potential treatment of human immunodeficiency virus (HIV). To date, more than 2,800 patients have been enrolled in these HIV clinical trials, including more than 1,000 patients in an expanded access program for HIV infected patients in need of new treatment options. During these clinical trials, the most common side effects reported with PREVEON have been dose-related gastrointestinal effects, including nausea and loss of appetite. In addition, elevations in serum creatinine and liver transaminsases have been reported.
Gilead Sciences is an independent biopharmaceutical company that seeks to provide accelerated 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 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.