Long-term Data Show Telbivudine (Tyzeka) Suppresses HBV Viral Load and Leads to HBeAg Clearance in Chronic Hepatitis B Patients

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At the 60th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD 2009) this month in Boston, researchers reported 4-year data from the GLOBE study, indicating that the nucleoside analog telbivudine (Tyzeka) continues to provide long-term viral load suppression, ALT normalization, and hepatitis B "e" antigen (HBeAg) seroconversion in chronic hepatitis B patients. Another study showed sustained response up to 2 years after completing telbivudine treatment.

GLOBE was an international Phase 3 trial comparing 600 mg/day telbivudine versus 100 mg/day lamivudine (Epivir-HBV) for 2 years in 1367 chronic hepatitis B patients with compensated liver disease.

As previously reported, at the end of the randomized part of the study, participants taking telbivudine were significantly more likely to experience treatment response than those taking lamivudine, with 63% of HBeAg positive patients and 78% of HBeAg negative patients achieving undetectable HBV DNA.

After completion of the randomized part of the trial, participants were given the option to continue telbivudine treatment for a further 2 years in an open-label extension study to evaluate the drug's long-term safety and efficacy. Y. Wang and colleagues presented 4-year results at the AASLD meeting (abstract 482).

A total of 426 telbivudine recipients (236 HBeAg positive and 190 HBeAg negative) elected to continue in the extension study. None had genotypic resistance to telbivudine at the end of the initial trial. Of these patients, 355 (83%) completed 4 years of therapy. The per-protocol population consisted of 398 patients (213 HBeAg positive and 185 HBeAg-negative).

Results

These findings led the investigators to conclude, "In HBeAg positive and HBeAg negative chronic hepatitis B patients, 4 years of telbivudine treatment provides effective viral suppression and ALT normalization with a favorable safety profile."

Moreover, they added, "telbivudine achieves a high seroconversion rate in HBeAg positive patients."

HBsAg as a Predictive Factor

In a related study (abstract 487), German researchers investigated serum hepatitis B surface antigen (HBsAg) levels over 3 years of telbivudine treatment in 162 HBeAg positive and 143 HBeAg negative patients who completed the telbivudine arm of the GLOBE trial, achieved undetectable HBV DNA, and were enrolled in the extension study for at least 52 weeks.

Results

Based on these findings, the investigators concluded, "Baseline serum HBsAg correlates with HBV DNA levels in HBeAg positive and HBeAg negative patients."

"Telbivudine treatment reduces serum HBsAg levels in HBeAg positive and HBeAg negative chronic hepatitis B patients," they continued. "Rapid on-treatment HBsAg decline of > 0.5 log10 IU/mL up to week 24 is highly predictive of future HBsAg clearance."

Post-treatment Outcomes

Finally, Chinese researchers looked at sustained post-treatment outcomes up to 2 years after patients completed treatment with telbivudine (abstract 424).

The analysis included 22 participants (17 HBeAg positive and 5 HBeAg negative) who received 600 mg/day telbivudine for 104 weeks.

Complete response for initially HBeAg positive patients was defined as undetectable HBV DNA, ALT normalization, and HBeAg seroconversion. For initially HBeAg patients, completed response was defined as undetectable HBV DNA and ALT normalization.

Patients who demonstrated complete response for at least 24 weeks could discontinue treatment and were followed for 2 years post-treatment. Serum HBV DNA and HBsAg levels were assessed at baseline, during treatment at weeks 24, 52, and 104, and during post-treatment follow-up.

Results

"On-treatment serum HBsAg levels are highly predictive of SVR to telbivudine at 2 years off treatment," the researchers concluded. "Quantitative serum HBsAg levels at treatment weeks 24 and 52 were more predictive of SVR to telbivudine than serum HBV DNA levels in these patients."

11/20/09

References

Y Wang, S Thongsawat, EJ Gane, and others.
Efficacy and Safety Outcomes After 4 Years of Telbivudine Treatment in Patients with Chronic Hepatitis B (CHB). 60th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD 2009). Boston. October 30-November 1, 2009. Abstract 482.

K Wursthorn, M Jung, MP Manns, and others. Different Kinetics of Serum HBsAg Decline in HBeAg-Positive vs HBeAg-Negative Patients During 3 Years of Telbivudine Treatment in Chronic Hepatitis B (CHB). 60th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD 2009). Boston. October 30-November 1, 2009. Abstract 487.

W Cai, Q Xie, X Zhou, and others.
On-treatment Serum HBsAg Level at 2 Years: Strong Predictor of Sustained Virologic Response to Telbivudine for up to 2 Years Off-treatment in Chronic Hepatitis B Patients. 60th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD 2009). Boston. October 30-November 1, 2009. Abstract 424.