October 28, 2003
Gilead Announces 144-Week Data of Hepsera in Patients Co-Infected With HIV And Lamivudine-Resistant HBVData Presented at 54th Annual Meeting of the American Association for the Study of Liver Diseases
BOSTON, Oct 28, 2003 (BUSINESS WIRE) -- Gilead Sciences (Nasdaq:GILD) today announced that treatment with its once-daily, oral antiviral agent Hepsera(R) (adefovir dipivoxil 10 mg) was associated with sustained reductions in levels of hepatitis B virus (HBV) DNA through 144 weeks (approximately three years) among patients chronically infected with lamivudine-resistant HBV and co-infected with HIV. Data from the single-center, open-label clinical trial (Study 460i) were presented today at the 54th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD) in Boston, Massachusetts by Yves Benhamou, MD, Service d'Hepato-Gastroenterologie, Groupe Hospitalier Pitie-Salpetriere, Paris, France. This presentation is one of eight Hepsera-related abstracts featured at the conference.
"Patients co-infected with HIV and HBV can be difficult to treat. The development of resistance - which emerges in up to 90 percent of immunocompromised HBV-infected patients after four years of therapy with lamivudine - can lead to progression of chronic hepatitis B," said Dr. Benhamou. "In this study, co-infected patients who received Hepsera showed sustained suppression of HBV through nearly three years of therapy."
About Study 460I
Study 460i is a single-center, open-label study of Hepsera in chronic hepatitis B patients with lamivudine-resistant HBV and co-infected with HIV. The study enrolled 35 patients with controlled HIV infection (mean baseline HIV RNA serum level of 2.88 log(10) copies/mL by Roche Amplicor Monitor PCR) who were receiving lamivudine 150 mg twice daily as part of their combination anti-HIV treatment regimen for a median of 42.3 months prior to enrollment. Lamivudine-resistant HBV (confirmed "YMDD" mutation) was detected in patients a median of 21.3 months prior to initiating treatment with Hepsera. The median baseline serum HBV DNA level in these patients was 8.75 log(10) copies/mL (Roche Amplicor(TM) Monitor PCR).
Hepsera was associated with a significant and progressive change from baseline in median serum HBV DNA levels after 144 weeks of treatment: -5.45 log(10) copies/mL (n=29; p less than 0.001) at week 144, compared with -4.0 log(10) copies/mL at week 48 and -4.8 log(10) copies/mL at week 96. Approximately 46 percent of patients had undetectable HBV DNA levels (less than 3.0 log(10) copies/mL) after nearly three years of therapy. By week 144, two patients had experienced HBeAg seroconversion.
Levels of serum alanine aminotransferase (ALT) - a measure of liver damage - also continued to decrease toward normal values throughout the study. At 144 weeks, 61 percent of patients had normal ALT levels. The median ALT was 31 IU/L, a further improvement from 96 weeks (46 IU/L), 48 weeks (53 IU/L) and a significant decline from the pre-study value (81 IU/L; p less than 0.001).
There were a total of three serious adverse events reported, all of which were determined to be unrelated to study drug. Two patients with transient changes in serum creatinine (greater than or equal to 0.5 mg/dL increases from baseline) were reported, both events resolved on continued treatment, and no patients had serum phosphorus levels less than 1.5 mg/dL, both laboratory markers of renal function. No adefovir-associated HBV resistance mutations (rtN236T) related to Hepsera treatment were identified through week 144.
Hepsera, the first nucleotide analogue for chronic hepatitis B, is administered as a once-daily 10 mg tablet and works by blocking HBV DNA polymerase, an enzyme involved in the replication of the virus in the body. In clinical trials and expanded access programs, approximately 7,000 patients have been treated with Hepsera for periods of up to three years. Hepsera is now available in the United States, the United Kingdom, France, Germany, Portugal, Ireland, Greece, Spain, Norway, Austria and Sweden. In April 2002, Gilead signed a licensing agreement with GlaxoSmithKline (GSK), granting GSK rights to commercialize Hepsera in Asia, Latin America and other territories.
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 in the first 48 weeks in Hepsera pivotal clinical studies were asthenia (weakness), 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 and post-treatment exacerbations of hepatitis, use in patients with underlying renal impairment or patients co-infected with HIV, and occurrence of nucleoside analogue-associated lactic acidosis and severe hepatomegaly with steatosis.
Chronic Hepatitis B
Worldwide, approximately 400 million people are chronically infected with hepatitis B, of which approximately one million die each year from complications of the disease, making chronic hepatitis B one of the 10 most common causes of death. Complications of chronic hepatitis B include cirrhosis (scarring of the liver), liver failure and liver cancer. Between one quarter and one third of people with chronic hepatitis B are expected to develop progressive liver disease.
About Gilead Sciences
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 the United States, 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 including the risk that in a clinical setting or through longer treatment periods Gilead may not continue to observe the safety, tolerability and resistance data in these trials. These risks, uncertainties and other factors could cause actual results to differ materially from those referred to in the forward-looking statements. The reader is cautioned not to rely on these forward-looking statements. These and other risks are described in detail in the Gilead Annual Report on Form 10-K for the year ended December 31, 2002 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(R) is a registered trademark of Gilead Sciences, Inc.
For complete prescribing information, please visit www.hepsera.com.
For more information on Gilead Sciences, please visit the company's web site at www.gilead.com or call Gilead Public Affairs at 1-800-GILEAD-5 or 1-650-574-3000.
SOURCE: Gilead Sciences
Gilead Sciences Susan Hubbard, 650-522-5715 (Investors) Erin Edgley, 925-683-9622 (Media)
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