JNJ-73763989 and bersacapavir treatment in nucleos(t)ide analogue-suppressed patients with chronic hepatitis B: REEF-2

作者：Kosh Agarwal, Marı́a Buti, Florian van Bömmel, Pietro Lampertico, Ewa Janczewska, Marc Bourlière, Thomas Vanwolleghem, Oliver Lenz, Thierry Verbinnen, Thomas N. Kakuda, Cristiana Mayer, John Jezorwski, Daniel G. Muenz, Maria Beumont, Ronald Kalmeijer, Michael Biermer, Isabelle Lonjon‐Domanec · 发表于：Journal of Hepatology · 年份：2024 · DOI：10.1016/j.jhep.2024.03.046 · 被引用次数：52 · 研究领域：Hepatitis B Virus Studies、RNA Interference and Gene Delivery、Hepatitis C virus research

BACKGROUND & AIMS: Functional cure for chronic hepatitis B (CHB) requires finite treatment. Two agents under investigation with the goal of achieving functional cure are the small-interfering RNA JNJ-73763989 (JNJ-3989) and the capsid assembly modulator JNJ-56136379 (JNJ-6379; bersacapavir). METHODS: REEF-2, a phase IIb, double-blind, placebo-controlled, randomized study, enrolled 130 nucleos(t)ide analogue (NA)-suppressed hepatitis B e-antigen (HBeAg)-negative patients with CHB who received JNJ-3989 (200 mg subcutaneously every 4 weeks) + JNJ-6379 (250 mg oral daily) + NA (oral daily; active arm) or placebos for JNJ-3989 and JNJ-6379 +active NA (control arm) for 48 weeks followed by 48 weeks off-treatment follow-up. RESULTS: IU/ml in 81.5% vs. 12.5% of patients in the active and control arms, respectively, and 38/81 (46.9%) patients in the active arm achieved HBsAg <100 IU/ml vs. 6/40 (15.0%) patients in the control arm. Off-treatment HBV DNA relapse and alanine aminotransferase increases were less frequent in the active arm, with 7/77 (9.1%) and 11/41 (26.8%) patients in the active and control arms, respectively, restarting NAs during follow-up. CONCLUSIONS: Finite 48-week treatment with JNJ-3989 + JNJ-6379 + NA resulted in fewer and less severe post-treatment HBV DNA increases and alanine aminotransferase flares, and a higher proportion of patients with off-treatment HBV DNA suppression, with or without HBsAg suppression, but did not result in functional cure. IMPACT AND I...