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48-Week Data Presented at 53rd Annual Meeting of the American Association for the Study of Liver Diseases
Results of the study show that patients with lamivudine-resistant virus who switched to Hepsera monotherapy or added Hepsera to ongoing lamivudine experienced significant virological, biochemical and serological improvements through 48 weeks. Patients receiving Hepsera alone or in combination with lamivudine experienced statistically significant reductions in both serum hepatitis B virus (HBV) DNA and alanine aminotransferase (ALT, a measure of liver damage), compared with patients who received lamivudine only. Patients treated with lamivudine alone did not show significant virological, biochemical or serological benefit compared with their baseline values. The results in the two Hepsera treatment arms shows switching to monotherapy with Hepsera achieved similar results to combination therapy (when Hepsera was added to lamivudine) in patients with lamivudine-resistant HBV.
"These data extend the results seen at 16 weeks through 48 weeks of therapy, indicating that adefovir dipivoxil (Hepsera), whether used alone or in combination with lamivudine, significantly reduces HBV DNA and normalizes ALT levels in chronic hepatitis B patients with lamivudine-resistant virus," said Dr. Peters. "Resistance to lamivudine has been shown to develop in approximately two thirds of patients after four years of therapy. The results of this study are particularly important as physicians consider the best approach to selecting treatment for their patients and for managing those who have developed resistance to lamivudine."
Study 461 Design
Patients were randomized (1:1:1) to three study groups receiving 1) Hepsera in combination with placebo, 2) addition of Hepsera in combination with lamivudine 100 mg, or 3) continuation of lamivudine 100 mg in combination with placebo. The primary endpoint for the study was the time-weighted average change from baseline in serum HBV DNA up to 16 weeks of treatment (DAVG16). Secondary end points evaluated the time-weighted average change from baseline in serum HBV DNA up to week 48 (DAVG48) and the change from baseline in serum levels of HBV DNA at 16 and 48 weeks in each treatment arm. Additionally, the study evaluated the proportion of patients whose ALT levels had returned to normal and the proportion of patients with HBeAg loss and HBeAg seroconversion after 48 weeks of treatment.
Study 461 Efficacy and Safety Results
Three patients withdrew from this study; one pre-treatment, one at week 44 due to progression of disease and one due to non-compliance. The most common adverse events reported were asthenia, abdominal pain and pharyngitis, and the frequency and type of adverse events were similar among all treatment arms. Five serious adverse events were reported, none of which were determined to be related to study drug. Through 48 weeks, no patients in this study had elevations in serum creatinine greater than or equal to 0.5 mg/dL from baseline, as confirmed by two consecutive laboratory assessments.
Summary of Results
Lamivudine Lamivudine+Hepsera Hepsera
(n=19) (n=20) (n=19)
----------------------------------------------------------------------
HBV DNA (log10 copies/mL) 0.05 -2.93 (p less than -3.06 (p
DAVG48 0.001) less than
(p-value) 0.001)
----------------------------------------------------------------------
Median change from baseline 0.0 -3.6 (p less than -4.0 (p less
for serum HBV DNA at week 0.001) than 0.001)
48 (log10 copies/mL) (p-
value)
----------------------------------------------------------------------
Proportion of patients 5 percent 53 percent (p less 47 percent
with ALT normalization at than 0.01) (p less
week 48 (p-value) than 0.01)
----------------------------------------------------------------------
Seroconversion 0 percent 6 percent 11 percent
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About Hepsera
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. This indication is based on histological, virological, biochemical and serological responses in adult patients with HBeAg-positive and HBeAg-negative chronic hepatitis B with compensated liver function, and in adult patients with clinical evidence of lamivudine-resistant hepatitis B virus with either compensated or decompensated liver function.
Safety Profile
Additional adverse events reported in pre- and post-liver transplant patients include fever, vomiting, hepatic failure, increases in ALT and AST levels, abnormal liver function, increased cough, pharyngitis, sinusitis, pruritus, rash, increases in serum creatinine, renal failure and renal insufficiency. Thirteen percent of patients (41 of 324) developed an elevation in serum creatinine greater than or equal to 0.5 mg/dL from baseline and 26 percent developed an increase greater than or equal to 0.3 mg/dL through 48 weeks. The contribution of Hepsera to changes in serum creatinine is difficult to assess as the majority of these patients had some degree of underlying renal insufficiency at baseline and other risk factors for renal dysfunction during treatment. These patients should be carefully monitored and may require dose interval adjustments.
As is the case with other antiviral therapies for chronic hepatitis B, physicians need to monitor liver function for exacerbation of hepatitis following discontinuation of therapy. Additionally, HIV resistance may emerge in chronic hepatitis B patients with unrecognized or untreated HIV infection who receive anti-hepatitis B therapies that may have activity against HIV. Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogues alone or in combination with other antiretrovirals.
About Hepatitis B
Hepatitis B is spread through infected blood or body fluids, sexual contact, injection drug use or perinatally from mother to child. Early symptoms include loss of appetite, fever, generalized aches and pains, fatigue, itching, urticaria (hives) and joint pain. Later symptoms may include nausea and vomiting, halitosis (bad breath), dark brown urine, jaundice (yellowing of the skin and eyes) and right-sided abdominal pain (especially with external pressure or palpitation).
About Gilead Sciences
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. 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, 2001 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 trademark of Gilead Sciences, Inc.
CONTACT: Gilead Sciences
Susan Hubbard, 650/522-5715 (Investors)
Erin Edgley, 650/522-5635 (Media)
http://www.gilead.com
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