Telbivudine May Be More Effective Than Lamivudine for Chronic Hepatitis B

Laurie Barclay
December 19, 2007 — Although lamivudine is the most widely prescribed anti–hepatitis B agent, telbivudine may be more effective than lamivudine for chronic hepatitis B virus (HBV) infection, according to the results of a double-blind, phase 3 trial reported in the December 20 issue of the New England Journal of Medicine.
"Reducing hepatitis B virus (HBV) replication to minimal levels is emerging as a key therapeutic goal for chronic hepatitis B," write Ching-Lung Lai, MD, from the University Department of Medicine, Queen Mary Hospital in Hong Kong, and colleagues from the Globe Study Group. "Telbivudine (β-L-2′-deoxythymidine) is an orally bioavailable L-nucleoside with potent and specific anti-HBV activity. In preclinical toxicologic testing, telbivudine had no mutagenic or carcinogenic effects and no appreciable embryonic or fetal toxic effects — findings that are particularly relevant for men and women in their reproductive years."
In the Globe trial, 1370 patients with chronic HBV infection were randomized to receive 600 mg of telbivudine or 100 mg of lamivudine once daily. This was a noninferiority trial of telbivudine to lamivudine for therapeutic response, defined as a reduction in serum HBV DNA levels to less than 5 log10 copies/mL, as well as loss of hepatitis B e antigen (HBeAg) or normalization of alanine aminotransferase levels. Secondary efficacy endpoints were histologic response, changes in serum HBV DNA levels, and HBeAg responses.
Compared with patients receiving lamivudine, a greater proportion of patients with positive HBeAg who were receiving telbivudine had a therapeutic response (75.3% vs 67.0%; P = .005) or a histologic response (64.7% vs 56.3%; P = .01) at week 52. In patients with negative HBeAg, telbivudine was also not inferior to lamivudine for therapeutic or histologic response.
In both the HBeAg-negative and HBeAg-positive groups, telbivudine was superior to lamivudine for several outcome measures, including mean reduction from baseline in the number of copies of HBV DNA, the proportion of patients with a decrease in HBV DNA to levels undetectable by polymerase-chain-reaction assay, and development of drug resistance.
"Among patients with HBeAg-positive chronic hepatitis B, the rates of therapeutic and histologic response at 1 year were significantly higher in patients treated with telbivudine than in patients treated with lamivudine," the study authors write. "In both the HBeAg-negative and the HBeAg-positive groups, telbivudine demonstrated greater HBV DNA suppression with less resistance than did lamivudine."
In laboratory abnormalities, elevated creatine kinase levels were more frequently reported in patients who received telbivudine, but elevated alanine aminotransferase and aspartate aminotransferase levels were more frequently reported in patients who received lamivudine.
"The multiple therapeutic choices now available for hepatitis B will enhance the ability of clinicians to maintain long-term control of HBV replication, ultimately improving clinical outcomes for more patients," the study authors conclude. "These results support telbivudine as an effective therapy for patients with chronic hepatitis B."
Idenix Pharmaceuticals, which employs or formerly employed 3 of the study authors, and Novartis Pharmaceuticals supported this study. Some of the other study authors have disclosed various financial relationships with Bristol-Myers Squibb, Idenix Pharmaceuticals, GlaxoSmithKline, Novartis Pharmaceuticals, Roche, Schering-Plough, SciClone Pharmaceuticals, Gilead Sciences, Debio, Vertex Pharmaceuticals, Human Genome Sciences, Pharmasett, Metabasis Therapeutics, and Chiron Corporation.
N Engl J Med. 2007;357:2576-2588.