Pharmacokinetics of JNJ‐73763989 and JNJ‐56136379 (Bersacapavir) in Participants With Moderate Hepatic Impairment

Abstract

AbstractJNJ‐73763989 is comprised of 2 short interfering RNAs (siRNAs), JNJ‐73763976 and JNJ‐73763924, that target hepatitis B virus (HBV) mRNAs for degradation, thereby inhibiting HBV replication. JNJ‐56136379 is a capsid assembly modulator that inhibits HBV replication by inducing the formation of empty capsids (CAM‐E). In 2 phase 1, open‐label, non‐randomized, single‐center studies, the single‐dose pharmacokinetics, safety, and tolerability of JNJ‐73763989 or JNJ‐56136379 were assessed in participants with moderate hepatic impairment (Child–Pugh Class B) versus participants with normal liver function. Participants in both studies received a single subcutaneous dose of JNJ‐73763989 200 mg or oral JNJ‐56136379 250 mg, followed by an evaluation of plasma pharmacokinetic parameters and safety assessments. Plasma exposure to JNJ‐73763976, JNJ‐73763924, and JNJ‐56136379 was 1.3‐ to 1.4‐, 1.8‐ to 2.2‐, and 1.1‐ to 1.3‐fold higher in participants with moderate hepatic impairment versus participants with normal liver function; however, these increases were not considered clinically relevant. Both drugs were well tolerated and safe, with 7 (21.9%) participants experiencing 1 or more treatment‐emergent adverse events, 3 of which were related to JNJ‐56136379. Overall, the plasma exposures of JNJ‐73763989 and JNJ‐56136379 were higher in participants with moderate hepatic impairment, but both were well tolerated. Further studies are needed to evaluate the effect of hepatic impairment under multiple‐dose administration.