Telbivudine (Tyzeka) Superior to Adefovir (Hepsera) at 52 Weeks

By Liz Highleyman

In an attempt to improve long-term response rates, researchers have studied a variety of nucleoside/nucleotide analog antiviral agents active against hepatitis B virus (HBV), alone and in various sequences and combinations.

As reported in the December 4, 2007 Annals of Internal Medicine, an international team of researchers compared the antiviral efficacy of telbivudine (Tyzeka) and adefovir dipivoxil (Hepsera), as well as the effect of switching from adefovir to telbivudine, in hepatitis B “e” antigen (HBeAg) positive chronic hepatitis B patients.

In this randomized, controlled, open-label trial conducted at 16 outpatient clinics, 135 treatment-naive HBeAg positive patients were randomly assigned in a 1:1:1 manner to receive:

• 52 weeks of telbivudine (Group A);

• 52 weeks of adefovir (Group B);

• 24 weeks of adefovir then telbivudine for the remaining 28 weeks (Group C).

The primary efficacy comparison was serum HBV DNA reduction at week 24, with a secondary comparison at week 52.

Results

• 131 patients completed 52 weeks of treatment.

• At week 24, the mean HBV DNA reduction was greater in Group A than in pooled Groups B and C (6.30 vs 4.97 log₁₀ copies/mL; difference, 1.33 log₁₀ copies/mL; P < 0.001).

• More participants in Group A had undetectable HBV DNA by polymerase chain reaction (39% vs 12%; odds ratio 4.46; P = 0.001).

• At week 52, the mean residual HBV DNA level was lower in Group A and Group C than in Group B (3.01, 3.02, and 4.00 log₁₀ copies/mL, respectively; difference 0.99 and 0.98 log₁₀ copies/mL; P = 0.004).

• Adverse events were similar across treatment groups, the most common being upper respiratory symptoms, headache, back pain, and diarrhea.

Conclusion

“Telbivudine demonstrated greater and more consistent HBV DNA suppression than adefovir after 24 weeks of treatment,” the authors concluded. “After 52 weeks, HBV DNA suppression was greater in patients who had received continuous telbivudine or were switched to telbivudine after 24 weeks than in those who received continuous adefovir.”

In an accompanying editorial, Jordan J. Feld and Marc G. Ghany of the National Institute of Diabetes, Digestive and Kidney Diseases discussed the growing complexity of hepatitis B treatment as new agents are approved.

“In the past decade, physicians treating chronic hepatitis B have gained the luxury of choice,” they wrote, noting that the U.S. Food and Drug Administration has now approved 6 drugs for chronic hepatitis B treatment

”Although therapy has improved over the past decade and most patients with chronic hepatitis B respond to treatment, rates of sustained response and HBsAg loss remain poor,” they added. “Therefore, we urgently need new drugs aimed at novel antiviral targets if we are to achieve HBsAg loss and successfully prevent and manage resistance. Until then, studies should focus on optimizing currently available drugs by finding the best regimen to treat chronic hepatitis B and the appropriate measures for changing or discontinuing therapy.”

01/04/08

References

HL Chan, EJ Heathcote, P Marcellin, and others. Treatment of hepatitis B e antigen positive chronic hepatitis with telbivudine or adefovir: a randomized trial. Annals of Internal Medicine 147(11): 745-54. December 4, 2007

JJ Feld and MG Ghany. Evolution of therapy for chronic hepatitis B: progressing from the simple to the complex. Annals of Internal Medicine 147(11): 806-808. December 4, 2007.