GLOBE Trial 2-Year Data Shows Telbivudine (Tyzeka) Is More Effective than Lamivudine (Epivir-HBV) for Chronic Hepatitis B

By Liz Highleyman

Several nucleoside/nucleotide analog agents have activity against hepatitis B virus (HBV), but the development of drug resistance can be a barrier to long-term treatment success. Newer agents, however, appear to produce more durable benefit than the old standard-of-care, lamivudine (Epivir-HBV).

Telbivudine (Tyzeka) was approved by the U.S. Food and Drug Administration in October 2006. Approval was based in part on 52-week data from the pivotal GLOBE trial. Follow-up continued, and now 104-week safety and efficacy findings have been published in the February 2009 issue of Gastroenterology.

Briefly, GLOBE was an international Phase 3 trial comparing 600 mg/day telbivudine versus 100 mg/day lamivudine over 2 years in 1367 chronic hepatitis B patients with compensated liver disease. Response was defined as HBV DNA < 5 log10 copies/mL and either HBeAg loss or normalization of alanine aminotransferase (ALT). After 1 year, among 921 hepatitis B "e" antigen (HBeAg) positive patients, the response rate was 75% in the telbivudine arm versus 67% in the lamivudine arm. Among 446 HBeAg negative patients, the corresponding rates were 75% and 77%.

Results

After 2 years of follow-up, telbivudine efficacy remained superior to that of lamivudine.

Among HBeAg positive participants, in an intent-to-treat analysis, the response rate was 63% in the telbivudine arm compared with 48% in the lamivudine arm (P < 0.001).

Among HBeAg negative patients, the corresponding rates were 78% and 66%, respectively (P = 0.007).

HBeAg positive patients in the telbivudine arm were more likely than lamivudine recipients to achieve undetectable HBV DNA < 300 copies/mL (55.6% vs 38.5%; P < 0.001) and HBeAg loss (35.2% vs 29.2%; P = 0.056).

However, HBeAg positive telbivudine recipients were less likely than lamivudine recipients to develop viral resistance (25.1% vs 39.5%; P < 0.001).

HBeAg seroconversion occurred in 29.6% of telbivudine recipients compared with 24.7% of lamivudine recipients overall, not a statistically significant difference (P = 0.095).

Among participants with baseline ALT > 2 x normal, however, the 36.0% vs 27.0% difference did reach significance (P = 0.022).

Similarly, among HBeAg negative participants, 82.0% of telbivudine recipients achieved undetectable HBV viremia compared with 56.7% of lamivudine recipients (P < 0.001).

Here again, drug resistance developed less often in the telbivudine arm (10.8% vs 25.9%; P < 0.001).

Overall, adverse events occurred with similar frequency in both treatment arms.

However, severe (grade 3-4) increases in creatine kinase levels -- a marker of possible muscle damage -- were significantly more common in the telbivudine arm (12.9% vs 4.1%; P < 0.001).

Multivariate logistic regression analysis identified telbivudine treatment, among other variables, as an independent predictor of better week 104 outcomes, leading the investigators to conclude, "Telbivudine is superior to lamivudine in treating patients with chronic hepatitis B over a 2-year period."

2/27/09

Reference
YF Liaw, E Gane, N Leung, and others. 2-Year GLOBE Trial Results: Telbivudine Is Superior to Lamivudine in Patients With Chronic Hepatitis B. Gastroenterology 136(2): 486-495. February 2008. (Abstract).