Efficacy and safety evaluation of tenofovir alafenamide against hepatitis B virus
Tenofoviral afenamide is a newly synthesized tenofovir phosphorylated prodrug with better plasma stability than tenofovir disoproxil fumarate (TDF) and maintains maximum integrity after entry into HBV-infected cells . A recent study published in the Journal of hepatology assesses antiviral efficacy, safety, and pharmacokinetics of tenofovir alafenamide.
Non-cirrhotic, untreated patients with chronic hepatitis B were randomly assigned to receive tenofovir alafenamide 8 mg, 25 mg, 40 mg, 120 mg, or 300 mg TDF for a period of 28 days at randomization (1: 1: 1: 1: 1). Assess safety, anti-virological response and pharmacokinetics. Follow-up 4 weeks after treatment.
Fifty-one subjects were randomized and completed treatment. Groups generally matched well (67% men, 57% Asian, 53% HBeAg negative, mean HBV DNA approximately 6.0 loglO IU / ml). None of the subjects developed grade 3/4 serious adverse reactions. In the tenofovir alafenamide treatment group, changes in serum HBV DNA were similar at 4 weeks (tenofovir alafenamide 8 mg, 25 mg, 40 mg, and 120 mg respectively -2.81 log10 IU / ml, -2.55 log10 IU / ml, -2.19 log10 IU / ml and -2.76 log10 IU / ml) and also comparable to the control group (TDF 300 mg group -2.68 log10 IU / ml). The kinetics of decreased viral load in each group were similar. Pharmacokinetics of Tenofovir alafenamide is linear and dose-proportional. Relative to the TDF 300 mg group, a tenofovir alafenamide dose of ≤25 mg was associated with a ≥92% reduction in area under the average Tenofovir profile.
Tenofovir alafenamide is safe and well tolerated. In all doses of tenofovir alafenamide evaluated, HBV DNA levels decreased similarly to TDF. Tenofovir alafenamide 25 mg dose was selected for further study in Hepatitis B clinical trials.