In patients with chronic hepatitis B infection, investigational telbivudine (LdT), a newer nucleoside analog, showed significantly better antiviral activity than the old standby Epivir (lamivudine).

That’s the conclusion of researchers based on early data from the international GLOBE trial, a phase 3 study comparing the two HBV antivirals in both HBV e-antigen positive and negative patients.

One-year results of the international study of the nucleosides were presented by Ching-Lung Lai, M.D., of the University of Hong Kong on behalf of GLOBE investigators at the annual meeting of the American Association for the Study of Liver Diseases here.

Telbivudine, Dr. Lai said, “has the potential to reduce the serious complications associated with chronic hepatitis B, and telbivudine’s favorable safety and convenience profile in trials to date also may make it a promising treatment option for patients, including those requiring long-term therapy.”

The GLOBE study is a randomized, double-blind trial comparing oral telbivudine at 600 mg/day with oral Epivir at 100 mg/day in 1,367 adults with chronic hepatitis B from 112 clinical centers in Asia, Europe, and North America.

At the time of entry into the two-year study, patients had to be HB e-antigen positive (HBeAg+), indicating a high viral load and high risk of infectivity, have HBV DNA levels > 6 log10 copies mL, have alanine aminotransferase levels (ALT) 1.3-10 times the upper limit of normal, and have compensated liver disease.

The primary endpoint is therapeutic response, a composite endpoint comprising viral suppression (serum HBV DNA suppression below 100,000 copies/mL) with either improved liver disease markers (ALT normalization) or loss of detectable HBeAg.

The investigators found that HBeAg+ patients taking telbivudine had a mean reduction in HBV DNA of -6.5 log10 vs. -5.5 log10 among patients on lamivudine. (P<0.01).

Among HBeAg- patients, those taking telbivudine had a -5.2 log10 HBV DNA reduction, vs. -4.4 log10 with Epivir (P<0.01).

Among HBeAg+ patients, 60% of those on telbivudine had an e-antigen loss, compared with 40% of those on Epivir (p<0.01).

Among those who were HBeAg-, telbivudine treatment reduced HBV DNA to below detectable levels in 88%s, compared with 71% of those on Epivir.

Looking at the composite endpoint of therapeutic response in antigen-positive patients, the authors found that 75% of this group achieved a response, compared with 67% of those on Epivir (P<0.05).

Among e-antigen negative patients, slightly more patients on lamivudine had a therapeutic response 77%, vs. 75% for telbivudine (P value not given).

Adverse events were similar between the groups, and included upper respiratory infections and headache in about 12% in each group, and fatigue and nasopharyngitis in about 11% in each group.

More patients on lamivudine than telbivudine had serum ALT elevations (8% vs, 4%, respectively), but more patients on telbivudine had transient creatine kinase elevations not requiring treatment modification (9% vs 3% for Epivir).

Dr. Lai is a consultant for Idenix Pharmaceuticals of Cambridge, Mass., maker of telbivudine.

Primary source: AASLD