BOSTON — Entecavir, an investigational oral antiviral agent, “achieves superior histologic, virologic, and biochemical improvement” in patients with e-antigen-positive chronic hepatitis B virus infection, Robert Gish, M.D., reported at the annual meeting of the American Association for the Study of Liver Diseases.
In an international phase III study, 715 patients with chronic hepatitis B who were nucleoside naive and positive for hepatitis B e-antigen (HBeAg) were randomized to receive either entecavir 0.5 mg daily or lamivudine 100 mg daily for 1 year.
“The objective here is to prevent the progression of liver disease,” said Dr. Gish, medical director of the California Pacific Medical Center in San Francisco. The HBeAg wild-type strain accounts for 25%-40% of hepatitis B virus (HBV) cases.
At 48 weeks, histologic improvement had occurred in 72% of patients on entecavir, compared with 62% on lamivudine, a statistically significant difference. Histologic improvement was defined as a reduction in the Knodell necroinflammatory score of at least 2 points plus no worsening of Knodell fibrosis.
There was a significantly greater reduction in HBV DNA with entecavir than with lamivudine, with 70% of patients having unmeasurable virus levels (below 400 copies/mL) after 48 weeks on the investigational agent, compared with 38% on lamivudine. Mean HBV DNA viral log scores dropped 6.78 log10 copies/mL in the entecavir group and 5.46 log10 copies/mL in the control group. “This is unprecedented,” Dr. Gish commented. “I know of no other modality that suppresses the virus to this extent.”
No significant differences between the lamivudine and entecavir groups were found for the percentages of patients with seroconversion, normalization of ALT levels, or loss of HBeAg DNA.
The incidence of serious adverse events was low and equal in the two treatment arms at 7%. The most commonly reported adverse effects were headache (about 25% of both groups), upper respiratory infection (about 20% of all patients), cough in about 15%, nasopharyngitis in 14%, upper abdominal pain in 10%, fatigue in 10%, and fever in about 10%. Treatment was discontinued because of adverse events in 1% of patients on entecavir and 3% of patients on lamivudine.
Bristol-Myers Squibb Co. has submitted a new drug application to the U.S. Food and Drug Administration and a marketing authorization application to the European Medicines Evaluation Agency for entecavir that includes data from this and other phase III trials of the drug.