2026-04-17T10:56:41Zhttps://recercat.cat/oai/request

oai:recercat.cat:11351/119852025-10-24T10:37:20Zcom_2072_378070com_2072_378040col_2072_378092

00925njm 22002777a 4500 dc van Bömmel, Florian author Lampertico, Pietro author Janczewska, Ewa author Bourliere, Marc author Agarwal, Kosh author Buti Ferret, Maria author 2024-09-30T06:35:35Z 2024-09-30T06:35:35Z 2024-09 Bersacapavir; Finite therapy; Hepatitis B virus Bersacapavir; Hepatitis B crònica; Teràpia finita Bersacapavir; Hepatitis B crónica; Terapia finita 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 At follow-up Week 24, no patients achieved the primary endpoint of functional cure (off-treatment hepatitis B surface antigen [HBsAg] seroclearance). No patients achieved functional cure at follow-up Week 48. There was a pronounced on-treatment reduction in mean HBsAg from baseline at Week 48 in the active arm vs. no decline in the control arm (1.89 vs. 0.06 log10 IU/ml; p = 0.001). At follow-up Week 48, reductions from baseline were >1 log10 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 implications Achieving a functional cure from chronic hepatitis B (CHB) with finite treatments is a major unmet medical need. The current study assessed the rate of functional cure and clinical outcome after controlled nucleos(t)ide analogue (NA) withdrawal in patients with low levels of HBsAg induced by 48 weeks of treatment with the small-interfering RNA JNJ-3989 and the capsid assembly modulator JNJ-6379 plus NA vs. patients who only received NA treatment. Though functional cure was not achieved by any patient in either arm, the 48-week treatment regimen of JNJ-3989, JNJ-6379, and NA did result in more patients achieving pronounced reductions in HBsAg, with clinically meaningful reductions maintained for up to 48 weeks off all treatments, as well as fewer off-treatment HBV DNA increases and alanine aminotransferase flares. These findings provide valuable insights for future studies investigating potential finite treatment options, while the reported efficacy and safety outcomes may be of interest to healthcare providers making treatment decisions for patients with NA-suppressed HBeAg-negative CHB. ClinicalTrials.gov Identifier NCT04129554. http://hdl.handle.net/11351/11985 Avaluació de resultats (Assistència sanitària) Hepatitis B - Tractament Medicaments antivírics - Ús terapèutic Nucleòsids - Ús terapèutic DISEASES::Virus Diseases::DNA Virus Infections::Hepadnaviridae Infections::Hepatitis B::Hepatitis B, Chronic Other subheadings::Other subheadings::Other subheadings::/drug therapy CHEMICALS AND DRUGS::Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Anti-Infective Agents::Antiviral Agents ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT::Diagnosis::Prognosis::Treatment Outcome CHEMICALS AND DRUGS::Nucleic Acids, Nucleotides, and Nucleosides::Nucleosides ENFERMEDADES::virosis::infecciones por virus ADN::infecciones por Hepadnaviridae::hepatitis B::hepatitis B crónica Otros calificadores::Otros calificadores::Otros calificadores::/farmacoterapia TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS::diagnóstico::pronóstico::resultado del tratamiento COMPUESTOS QUÍMICOS Y DROGAS::acciones y usos químicos::acciones farmacológicas::usos terapéuticos::antiinfecciosos::antivíricos COMPUESTOS QUÍMICOS Y DROGAS::nucleótidos y nucleósidos de ácidos nucleicos::nucleósidos JNJ-73763989 and bersacapavir treatment in nucleos(t)ide analogue-suppressed patients with chronic hepatitis B: REEF-2