Adefovir Dipivoxil Reduces ALT & in HBV Levels...

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Adefovir Dipivoxil Produces Significant Reductions in ALT and in HBV Levels in Patients with Lamivudine-Resistant HBV Treatment with adefovir dipivoxil 10 mg as monotherapy or in combination with lamivudine produces significant reductions in both serum hepatitis B virus (HBV) DNA and alanine transaminase (ALT, a measure of liver damage) levels through 16 weeks in patients infected with lamivudine-resistant HBV. Treatment with lamivudine monotherapy in these patients was not associated with statistically significant reductions in HBV DNA or ALT levels. The data were discussed in an oral presentation (Abstract 646) at the 37 th Annual Meeting of the European Association for the Study of the Liver (EASL) in Madrid, Spain by Marion Peters, MD, Principal Investigator and Chief of Hepatology Research, University of California, San Francisco Medical Center. "These data indicate that adefovir dipivoxil, whether used alone or in combination with lamivudine, is active against HBV resistance mutations that develop in nearly one third of patients within one year of beginning treatment with lamivudine," said Dr. Peters. "The growing database from controlled clinical trials, including data presented earlier at this conference, suggest that treatment with adefovir dipivoxil significantly lowers serum HBV DNA and normalizes ALT levels. These results indicate that treatment with adefovir dipivoxil monotherapy may be a potential new therapeutic option for patients with chronic hepatitis B." About Study 461 Study 461 is an ongoing 48-week, randomized, double-blind, placebo-controlled, multicenter study of 59 patients in the United States, Europe, Australia and Canada. Participants had chronic hepatitis B with compensated liver disease and had received treatment with lamivudine monotherapy prior to enrollment. YMDD mutations in the HBV DNA polymerase, associated with lamivudine resistance, were present in all patients upon entry into the study. Patients were randomized to receive either adefovir dipivoxil 10 mg (n=20), a combination of adefovir dipivoxil 10 mg with lamivudine 100 mg (n=20) or lamivudine 100 mg (n=19). After 16 weeks, patients in both the adefovir dipivoxil monotherapy and combination adefovir dipivoxil and lamivudine groups achieved similar, significant median reductions in serum HBV DNA levels from baseline (2.86 log10 copies/mL vs. 2.87 log10 copies/mL, p<0.0001). In comparison, serum HBV DNA levels remained the same (no decrease, or change of 0.00 log10 copies/mL) in patients treated with lamivudine 100 mg monotherapy (p<0.001 vs. both the adefovir dipivoxil monotherapy and adefovir dipivoxil plus lamivudine treatment arms). In addition, ALT levels normalized in 42 percent of patients receiving combination adefovir dipivoxil and lamivudine (p=0.008) and in 32 percent of patients treated with adefovir dipivoxil monotherapy (p=0.04) compared to six percent of patients receiving lamivudine monotherapy. Serum HBV DNA and ALT levels both are markers of disease severity. The most common adverse events reported were asthenia, abdominal pain and pharyngitis, and the nature, severity and frequency of adverse events were similar among all treatment arms. Additional data from this study will be analyzed following 48 weeks of treatment. Study 461 Resistance Data Preliminary virology analyses from the first 32 weeks of Study 461 also were discussed in an oral presentation at the conference (Abstract 568) by Shelly Xiong, PhD, Gilead. At the end of the 32 weeks of treatment, 32 percent of patients who received adefovir dipivoxil monotherapy (n=20) lost the YMDD resistance mutation (a hallmark of lamivudine resistance) and reverted to wild-type HBV. No patients receiving lamivudine lost the YMDD resistance mutation. "Gilead is dedicated to advancing therapeutics for life-threatening diseases worldwide by seeking solutions to complex treatment issues, such as resistance, faced by physicians and their patients," said John C. Martin, PhD, President and CEO, Gilead. "The breadth of adefovir dipivoxil data presented this week at EASL underscores the potential this drug may have to address the urgent, unmet medical needs of patients suffering from chronic hepatitis B." 04/19/02 Source www.gilead.com References M Peters and others. ADEFOVIR DIPIVOXIL (ADV) ALONE AND IN COMBINATION WITH LAMIVUDINE (LAM) SUPPRESSES LAM-RESISTANT HEPATITIS B VIRUS (HBV) REPLICATION: 16 WEEK INTERIM ANALYSIS. Abstract 646. 37th Annual Meeting of the European Association for the Study of the Liver (EASL). April 18-22, 2002. Madrid, Spain. S Xiong and others. LOSS OF LAMIVUDINE RESISTANCE MUTATIONS AFTER PATIENTS SWITCHED TO ADEFOVIR DIPIVOXIL THERAPY. Abstract 568. 37th Annual Meeting of the European Association for the Study of the Liver (EASL). April 18-22, 2002. Madrid, Spain.