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Tenofovir disoproxil fumarate provides better HBV antiviral efficacy than adefovir dipivoxil, with similar safety, studies reveal

Friday, December 12 2008 | Comments

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What's This? Treatment with tenofovir disoproxil fumarate (DF), the oral prodrug of tenofovir, provides superior hepatitis B virus (HBV) antiviral efficacy with a similar safety profile relative to adefovir dipivoxil, according to data from a pair of Phase III trials.

To compare the safety and efficacy of tenofovir DF with that of adefovir dipivoxil in treating HBV infection, researchers conducted 2 Phase III studies in which patients with hepatitis B e antigen (HBeAg)-negative or HBeAg-positive chronic HBV infection received tenofovir DF 300 mg or adefovir dipivoxil 10 mg once daily on a double-blind basis for 48 weeks. The primary endpoint of the studies was a plasma HBV DNA level of <400 copies/mL and histologic improvement (defined as a reduction in the Knodell necroinflammation score of >=2 points without worsening fibrosis) at week 48.

In Study 102, 375 patients received >=1 dose of the assigned drug (tenofovir DF, n=250; adefovir dipivoxil, n=125); in Study 103, 266 patients received >=1 dose (tenofovir DF, n=176; adefovir dipivoxil, n=90).

In each of the studies, a significantly greater proportion of the patients who received tenofovir DF reached the primary endpoint of both an HBV DNA level <400 copies/mL and histologic improvement relative to the patients who received adefovir dipivoxil (71% vs 49%, respectively, among the HBeAg-negative patients and 67% vs 12% among the HBeAg-positive patients). However, histologic improvement was similar between the treatment groups.

Further, a significantly greater proportion of the HBeAg-positive patients (Study 103) who received tenofovir DF had normalized alanine aminotransferase levels (68% vs 54%; P=.03) and loss of HBV surface antigen (3.2% vs 0%; P=.02) at 48 weeks as compared with those who received adefovir dipivoxil.

The safety profiles of both drugs were in line with those observed in previous trials, and nausea was the only adverse event that consistently occurred more often among the patients who received tenofovir DF than among those who received adefovir dipivoxil.

"In patients with compensated chronic HBV infection, tenofovir DF was superior to adefovir dipivoxil with respect to the primary endpoint of antiviral efficacy," the study authors wrote.

"In light of its favorable long-term safety record in patients with HIV-1 infection, tenofovir DF should be considered for the treatment of chronic HBV infection," they concluded. (Marcellin P, et al. N Engl J Med 2008;359:2442-2455.)

The study was supported by Gilead Sciences Inc.

This information concerns a use that has not been approved by the Food and Drug Administration.

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