November 14, 2005
Five-Year Data Evaluating Long-Term Therapy with Hepsera(R) for Hepatitis B ''e'' Antigen-Negative Chronic Hepatitis B Presented at AASLD Annual Meeting
SAN FRANCISCO--(BUSINESS WIRE)--Nov. 14, 2005-- Data Indicate that Hepsera May Lead to Regression of Liver Fibrosis in Patients Treated for up to Five Years
Gilead Sciences (Nasdaq:GILD) today presented data describing the sustained efficacy and safety of its oral antiviral drug Hepsera(R) (adefovir dipivoxil) for up to five years of treatment among patients with hepatitis B "e" antigen-negative, presumed precore mutant chronic hepatitis B. In this analysis, which includes the first prospective set of liver biopsies following five years of oral antiviral therapy, treatment with Hepsera resulted in regression of liver fibrosis in 75 percent of patients. Liver fibrosis is a serious consequence of chronic liver inflammation. Study results were presented as a late breaker poster (#LB12) at the 56th American Association for the Study of Liver Diseases Annual Meeting in San Francisco, CA.
"This study offers long-term evidence of antiviral efficacy and clinical benefit among patients with a difficult-to-treat form of chronic hepatitis B," said Stephanos Hadziyannis, MD, Department of Medicine, Henry Dunant Hospital, Athens, Greece, and a lead investigator for Study 438. "Long-term therapy is often the rule for patients with HBeAg-negative hepatitis B, and other oral antiviral therapies either lack long-term data in this population or lead to the development of genotypic resistance at high rates after only a few years. The data presented indicate that Hepsera may be able to reverse signs of liver damage in patients who received up to five years of continuous treatment, with a relatively low rate of resistance."
Dr. Hadziyannis presented efficacy, tolerability, resistance and safety data from an open-label extension of Study 438, in which patients with HBeAg-negative chronic hepatitis B received Hepsera monotherapy continuously for up to 240 weeks.
Liver biopsies at years one, two, four and five (240 weeks) showed continual improvement in inflammation and regression of fibrosis. Eighty-three percent (20/24) and 75 percent (18/24) of patients showed improvement in inflammation and regression of fibrosis following 240 weeks of Hepsera treatment, respectively. Sixty-nine percent (38/55) of patients who received Hepsera for 240 weeks exhibited improvement in liver function, as measured by normalization of serum alanine transferase (ALT) levels. Sixty-seven percent (37/55) of patients had suppression of viral replication, indicated by undetectable levels of serum HBV DNA (less than 1,000 copies/mL). In addition, four patients experienced HBsAg loss. Three of the four patients showed sAg seroconversion (complete loss of HBsAg and the development of antibodies to the HB "surface" antigen) by the end of the evaluation. Data from this study also showed that biochemical, virologic, serological and histological results in the 240-week treatment group were similar to those in a separate cohort of patients treated with placebo for the first year and Hepsera monotherapy for four years (192 weeks), indicating that therapy with Hepsera is associated with sustained improvements in patients with HBeAg-negative chronic hepatitis B.
Two mutations (rtN236T and rtA181V) in the HBV polymerase enzyme have been associated with genotypic resistance to Hepsera. According to a life-table analysis, the cumulative probability of selecting these viral mutations with Hepsera was 0, 3, 11, 18 and 29 percent after 48, 96, 144, 192 and 240 weeks of treatment, respectively. These mutations are indicators of the potential for clinical breakthrough.
The safety profile of Hepsera remained favorable through 240 weeks of treatment. Four patients (3 percent) had a confirmed increase in serum creatinine of greater than or equal to 0.5 mg/dL from baseline by week 240 and of those one patient discontinued the study. One patient had a serum phosphorous level less than 2.0 mg/dL, which was observed after discontinuation of therapy. Serious adverse events were reported in 19 percent (24/125) of patients in the study; none were determined to be related to Hepsera. Three patients (2 percent) discontinued from the study due to adverse events.
Hepsera, a nucleotide analogue for the treatment of chronic hepatitis B, works by inhibiting HBV DNA polymerase, an enzyme involved in the replication of the virus in the body.
In the United States, Hepsera is indicated for the treatment of chronic hepatitis B in adults with evidence of active viral replication and either evidence of persistent elevations in serum aminotransferases (ALT or AST) or histologically active disease.
Clinical and laboratory evidence of exacerbations of hepatitis have occurred after discontinuation of treatment with antiviral therapies for hepatitis B, including Hepsera. Special warnings and precautions for use are included in the package insert regarding monitoring of renal function, post-treatment exacerbations of hepatitis, and the occurrence of lactic acidosis and severe hepatomegaly with steatosis. The adverse reactions considered at least possibly related to treatment reported in 3 percent or greater of patients in the first 48 weeks in Hepsera pivotal clinical studies were asthenia, headache, abdominal pain, nausea, flatulence, diarrhea and dyspepsia. Patients who received Hepsera beyond 48 weeks reported adverse reactions similar in nature and severity to those reported in the first 48 weeks of treatment with only a slight increase in incidence. By week 96, increases in serum creatinine were observed in patients with chronic hepatitis B and compensated liver disease treated with Hepsera. Changes in serum creatinine were more prevalent in patients pre- and post-transplantation with lamivudine-resistant liver disease and multiple risk factors for changes in renal function who were treated with Hepsera for up to 129 weeks, with a median time on treatment of 19 and 56 weeks, respectively. Dosing instructions for patients with underlying renal impairment and for patients co-infected with HIV are also provided in the package insert, which is available for download online at www.hepsera.com.
About Chronic Hepatitis B
Chronic hepatitis B is a serious disease that can lead to potentially fatal complications such as cirrhosis and liver cancer. More than 400 million people are estimated to be chronically infected with HBV worldwide, with approximately 1.25 million people infected in the United States alone. HBeAg-negative hepatitis B accounts for approximately 14 to 33 percent of chronic hepatitis B cases worldwide.
Gilead Sciences is a biopharmaceutical company that discovers, develops and commercializes innovative therapeutics in areas of unmet medical need. The company's mission is to advance the care of patients suffering from life-threatening diseases worldwide. Headquartered in Foster City, California, Gilead has operations in North America, Europe and Australia.
This press release includes forward-looking statements, within the meaning of the Private Securities Litigation Reform Act of 1995, that are subject to risks, uncertainties and other factors. These risks and uncertainties could cause actual results to differ materially from those referred to in the forward-looking statements. Risks are described in detail in the Gilead Annual Report on Form 10-K for the year ended December 31, 2004 and in Gilead's Quarterly Reports on Form 10-Q, all of which are on file with the U.S. Securities and Exchange Commission. All forward-looking statements are based on information currently available to Gilead and Gilead assumes no obligation to update any such forward-looking statements.
Hepsera is a registered trademark of Gilead Sciences, Inc.
For more information on Gilead, please call the Gilead Public Affairs Department at 1-800-GILEAD-5 (1-800-445-3235) or visit www.gilead.com.
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SOURCE: Gilead Sciences, Inc.