Press Releases
November 02, 2004
Gilead Announces Long-Term Safety and Efficacy Data, Through 144 Weeks, for Hepsera in Patients With Chronic Hepatitis B
Data Show Increasing Serologic, Virologic and Biochemical Response Over 144 Weeks in Treatment-Naive Hepatitis B "e" Antigen-Positive Patients
BOSTON--(BUSINESS WIRE)--Nov. 2, 2004-- Gilead Sciences (Nasdaq:GILD) today announced 144-week data from a clinical trial (Study 437) of its oral antiviral drug Hepsera(R) (adefovir dipivoxil 10 mg) in patients with hepatitis B "e" antigen-positive (HBeAg-positive) chronic hepatitis B virus (HBV). The "e" antigen is a viral protein found in the blood of many people infected with HBV. Study results were presented today at the 55th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD) in Boston, Massachusetts.
"Chronic hepatitis B is a challenging disease that often requires long-term therapy," said Patrick Marcellin, MD, head of the Claude Bernard Research Center on Viral Hepatitis, Service d'Hepatologie and INSERM Unit 481, Hopital Beaujon, Assistance Publique Hopitaux de Paris, Clichy; Professor Universite Paris VII, France, and a lead investigator in Study 437. "This study suggests that in first-line treatment, Hepsera offers tolerability, continued inhibition of viral replication and normalization of liver enzymes for up to 144 weeks, with an increasing percent of patients achieving HBeAg seroconversion."
Study 437 Design
The efficacy, tolerability and safety data up to 144 weeks from Study 437 were presented today by Professor Marcellin (Poster Presentation #1135). This randomized, double-blind, placebo-controlled clinical trial was designed to evaluate the safety and efficacy of Hepsera in patients with HBeAg-positive chronic hepatitis B. At baseline, patients were randomized to receive Hepsera (n=171) or placebo (n=167) for the first 48 weeks. Following 48 weeks, patients who were randomized to the placebo or Hepsera arm in year one were eligible to receive Hepsera. The study continues to evaluate the long-term safety and efficacy of Hepsera. Most Hepsera patients received one or more doses of placebo in the second year of the study due to a misallocation of dosing error.
144-week Study Results
Kaplan-Meier analyses were used to generate estimates of efficacy up to 144 weeks for all patients who had received at least one dose of Hepsera (n=309). Data are summarized in the table below.
TABLE
Efficacy Measurements Week 48 Week 96 Week 144
------------------------------------- ---------- ---------- ----------
(Kaplan-Meier estimates)
Percent HBV DNA undetectable(1) 28% 45% 56%
Percent Normalization of ALT(2) 58% 71% 81%
Percent HBeAg loss 21% 42% 51%
Percent HBeAg seroconversion(3) 12% 29% 43%
(1) Less than 1,000 copies/mL, Roche Amplicor Monitor(TM) PCR assay
(2) ALT (alanine aminotransferase) is an enzyme found in the liver;
elevated blood levels of ALT indicates liver disease
(3) Loss of HBeAg and development of anti-HBe antibodies
In a separate analysis, the long term safety of Hepsera was evaluated in patients who received continuous Hepsera treatment through 144 weeks (n=65). No patient had confirmed increases in serum creatinine of greater than or equal to 0.5 mg/dL from baseline or a serum phosphorus level less than 1.5 mg/dL, laboratory markers of renal function, as confirmed by two consecutive laboratory assessments. The safety profile over 144 weeks was consistent with that seen over the first 48 weeks, which was similar to placebo. In this study, the most common adverse events reported were asthenia, flu syndrome, abdominal pain and headache.
Long-term Data in Pre- and Post-Liver Transplantation
Data from Study 435, further profiling the long-term safety and efficacy up to 144 weeks of Hepsera treatment, were also presented today at AASLD by Dr. Eugene Schiff, University of Miami, Center for Liver Disease (Poster Presentation #1143). Study 435 was designed to evaluate Hepsera treatment in liver transplant patients with lamivudine-resistant HBV. The study included both pre-transplant patients (n=226) and post-transplant patients (n=241).
About Chronic Hepatitis B
Chronic hepatitis B is a serious disease caused by the hepatitis B virus (HBV), which attacks the liver. Chronic hepatitis B infection can lead to potentially fatal complications such as cirrhosis and liver cancer, and is one of the leading causes of death worldwide. More than 400 million people have chronic hepatitis B worldwide. Approximately 1.25 million people are chronically infected with HBV in the United States alone.
About Hepsera
Hepsera, a nucleotide analogue for the treatment of chronic hepatitis B, is administered as a once-daily 10 mg tablet and works by inhibiting HBV DNA polymerase, an enzyme involved in the replication of the virus in the body. Hepsera is now available in the United States and 16 countries in Europe. In April 2002, Gilead signed a licensing agreement with GlaxoSmithKline (GSK), granting to GSK rights to commercialize Hepsera in Asia, Latin America and other territories. Hepsera has now been approved in 15 countries in these regions.
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.
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. With extended treatment, mild to moderate increases in serum creatinine were observed uncommonly in patients with chronic hepatitis B and compensated liver disease treated with Hepsera for a median of 49 weeks and a maximum of 109 weeks. Changes in serum creatinine were observed very commonly in patients with pre- and post-transplantation 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. 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, use in patients with underlying renal impairment, patients co-infected with HIV, the occurrence of nucleoside analogue-associated lactic acidosis and severe hepatomegaly with steatosis.
About Gilead
Gilead Sciences is a biopharmaceutical company that discovers, develops and commercializes therapeutics to advance the care of patients suffering from life-threatening diseases worldwide. The company has seven marketed products, and focuses its research and clinical programs on anti-infectives. Headquartered in Foster City, CA, 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 that could cause actual results to differ materially from those referred to in the forward-looking statements. Such risks and uncertainties include the risk that the results observed in these 144-week data will not be observed through longer treatment periods and uncertainty regarding inclusion of these data in the Hepsera product label. These and other risks are described in detail in the Gilead Annual Report on Form 10-K for the year ended December 31, 2003 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 full prescribing information, please visit www.Hepsera.com.
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.
CONTACT: Gilead Sciences
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SOURCE: Gilead Sciences