Virology analysis of chronic hepatitis B virus–infected patients treated for 28 days with JNJ‐56136379 monotherapy

Four weeks of once‐daily oral JNJ‐56136379 (JNJ‐6379; 25, 75, 150 or 250 mg), a class‐N capsid assembly modulator (CAM‐N), was well tolerated with potent antiviral activity in treatment‐naïve, chronic hepatitis B e antigen–positive and hepatitis B e antigen–negative patients (NCT02662712). Hepatitis B virus (HBV) genome sequence analysis, using HBV DNA next‐generation sequence technology, was performed, and impact of substitutions on efficacy was assessed. Analyses focused on HBV core protein amino acid positions associated with JNJ‐6379 and/or other CAMs in vitro resistance, and those within the CAM‐binding pocket. 31/57 patients had ≥ 1 polymorphism at any of the core amino acid positions of interest, most frequently at positions 38 (32%), 105 (23%) and 109 (14%). None of these polymorphisms are known to reduce JNJ‐6379 in vitro activity (fold change [FC] in 50% effective concentration