The US Food and Drug Administration (FDA) announced yesterday that on March 29th it approved entecavir, marketed by Bristol-Myers Squibb (BMS) as Baraclude, for the treatment of chronic hepatitis B virus for individuals monoinfected with hepatitis B and individuals coinfected with both HIV and hepatitis B who have previously received 3TC (lamivudine, Epivir/Zeffix).
The approval for monoinfected patients is based on data after one year of treatment in nucleoside-treatment-naive and lamivudine-resistant adult patients with hepatitis B e antigen-positive, or hepatitis B e antigen-negative chronic hepatitis B infection with compensated liver disease.
The approval for coinfected patients is based on more limited data from a randomised, double-blind, placebo-controlled study (AI463038 also known as ETV-038) of entecavir versus placebo in 68 individuals coinfected with HIV and HBV who experienced recurrence of hepatitis B viral load while receiving a lamivudine-containing highly active antiretroviral (HAART) regimen.
During the first 24-weeks of this study, coinfected individuals continued their lamivudine-containing HAART regimen and were randomised to add either 1mg entecavir once daily (n=51) or placebo (n=17) for 24 weeks. Results of this part of the study were reported on aidsmap last month after being presented at the Twelfth Conference on Retroviruses and Opportunistic Infections held in Boston, Massachusetts. For approval purposes, the FDA also included data from the 24-week the open-label phase of the study where all participants received entecavir.
After 24 weeks, weeks the mean hepatitis B viral load fell 3.66 log10 copies/mL with entecavir while rising 0.11 log10 copies/mL in the placebo group. Among individuals assigned to receive entecavir, 6% had a hepatitis B viral load below 300 copies/mL compared with 0% on placebo. Thirty-four percent of participants on entecavir had ALT normalisation compared with 8% of patients in the placebo group.
Unlike the other drugs used in coinfection (3TC, adefovir, and tenofovir), entecavir has no activity against HIV. Median HIV viral load level remained stable at approximately 2 log10 copies/mL during the first 24 weeks of the study. This can be beneficial, since entecavir use cannot lead to HIV cross-resistance. In addition, entecavir does not interact with any of the protease inhibitors (PIs) or non nucleoside reverse transcriptase inhibitors (NNRTIs).
The recommended dose of entecavir for chronic hepatitis B virus infection in nucleoside treatment-naive adults and adolescents 16 years of age and older is 0.5 mg once daily. For those with a history of hepatitis B viraemia while receiving lamivudine or known lamivudine resistance mutations, the recommended dose is 1mg once daily.
Entecavir is also available in an oral Solution containing 0.05 mg of entecavir per millilitre: 10 mL of the oral solution provides a 0.5mg dose and 20 mL provides a 1mg dose of entecavir.
The FDA recommend that entecavir be taken on an empty stomach, at least two hours after a meal and two hours before the next meal).
Bristol-Myers Squibb filed for entecavir approval in the European Union last autumn.