IDDF2024-ABS-0270 Efficacy and safety of bulevirtide in combination with pegylated interferon alfa-2a in patients with chronic hepatitis delta: primary endpoint results from a phase 2b open-label, randomized, multicenter study MYR204

<h3>Background</h3> Bulevirtide (BLV) is a first-in-class entry inhibitor approved in the EU for the treatment of chronic HDV infection (CHD). This Phase 2 study (MYR204) evaluated the safety and efficacy of BLV with or without peginterferon alfa-2a (PegIFN) in patients with CHD and compensated liver disease. <h3>Methods</h3> 174 patients with CHD were randomized and stratified based on the absence or presence of compensated cirrhosis to receive (A) PegIFN for 48 weeks (w); (B) BLV 2mg + PegIFN or (C) BLV 10mg + PegIFN for 48w, both followed by 48w of monotherapy with BLV 2mg or 10mg, respectively; or (D) BLV 10mg for 96w. All patients were followed up for 48w after the end of treatment (EOT). The primary endpoint was sustained virologic response at W24 after EOT (SVR24), defined as undetectable HDV RNA with a predefined comparison between Arms C and D. <h3>Results</h3> Efficacy and safety results are shown in Table 1 (IDDF2024-ABS-0270 Table 1). SVR24 was achieved by 17% of Arm A, 30% of Arm B, 46% of Arm C, and 12% of Arm D (P=.0003; Arm C vs D). ALT normalization and composite endpoint at W24 after EOT were superior with BLV 10mg + PegIFN compared to monotherapy. HBsAg loss was only observed with the combination. The most common adverse events (AE) were leukopenia, neutropenia, thrombocytopenia, influenzalike illness, lymphopenia, and vitamin D deficiency. AEs observed in the BLV + PegIFN combination arms were similar to those with PegIFN monotherapy. BLV dose-dependent bile acid elevations were asymptomatic, and levels returned to baseline after EOT. 6 patients (3%) discontinued treatment; none were assessed as related to BLV. <h3>Conclusions</h3> In patients with compensated CHD, BLV in combination with PegIFN resulted in higher rates of SVR24 and ALT normalization vs BLV or PegIFN monotherapy. Combination therapy was well tolerated with AEs, which was consistent with PegIFN monotherapy.

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Published
2024-08-01
DOI
https://doi.org/10.1136/gutjnl-2024-iddf.195
Primary Topic
Hepatitis C virus research
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article
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article

IDDF2024-ABS-0270 Efficacy and safety of bulevirtide in combination with pegylated interferon alfa-2a in patients with chronic hepatitis delta: primary endpoint results from a phase 2b open-label, randomized, multicenter study MYR204

Vladimir Chulanov, Anu Osinusi, Marie‐Noëlle Hilleret, Tarik Asselah et al.
Hepatitis C virus research
article

IDDF2024-ABS-0270 Efficacy and safety of bulevirtide in combination with pegylated interferon alfa-2a in patients with chronic hepatitis delta: primary endpoint results from a phase 2b open-label, randomized, multicenter study MYR204

Vladimir Chulanov, Anu Osinusi, Marie‐Noëlle Hilleret, Tarik Asselah, Ştefan Lazăr, Marc Bourlière, Pavel Bogomolov, Renée-Claude Mercier, Tatyana Stepanova, Gheorghe Plăcintă, Dmitry Manuilov, V. Е. Syutkin, Olga Sagalova, Fabien Zoulim, В. Н. Городин, Vlad Ratziu, Victor Pântea, John Flaherty, George Sebastian Gherlan, Viacheslav Morozov, Audrey Lau, Ben L. Da, Lei Ye, Stanilas Pol, Pietro Lampertico, Jacques Yu, Adrian Streinu-Cercel, Heiner Wedemeyer
article en

Abstract

<h3>Background</h3> Bulevirtide (BLV) is a first-in-class entry inhibitor approved in the EU for the treatment of chronic HDV infection (CHD). This Phase 2 study (MYR204) evaluated the safety and efficacy of BLV with or without peginterferon alfa-2a (PegIFN) in patients with CHD and compensated liver disease. <h3>Methods</h3> 174 patients with CHD were randomized and stratified based on the absence or presence of compensated cirrhosis to receive (A) PegIFN for 48 weeks (w); (B) BLV 2mg + PegIFN or (C) BLV 10mg + PegIFN for 48w, both followed by 48w of monotherapy with BLV 2mg or 10mg, respectively; or (D) BLV 10mg for 96w. All patients were followed up for 48w after the end of treatment (EOT). The primary endpoint was sustained virologic response at W24 after EOT (SVR24), defined as undetectable HDV RNA with a predefined comparison between Arms C and D. <h3>Results</h3> Efficacy and safety results are shown in Table 1 (IDDF2024-ABS-0270 Table 1). SVR24 was achieved by 17% of Arm A, 30% of Arm B, 46% of Arm C, and 12% of Arm D (P=.0003; Arm C vs D). ALT normalization and composite endpoint at W24 after EOT were superior with BLV 10mg + PegIFN compared to monotherapy. HBsAg loss was only observed with the combination. The most common adverse events (AE) were leukopenia, neutropenia, thrombocytopenia, influenzalike illness, lymphopenia, and vitamin D deficiency. AEs observed in the BLV + PegIFN combination arms were similar to those with PegIFN monotherapy. BLV dose-dependent bile acid elevations were asymptomatic, and levels returned to baseline after EOT. 6 patients (3%) discontinued treatment; none were assessed as related to BLV. <h3>Conclusions</h3> In patients with compensated CHD, BLV in combination with PegIFN resulted in higher rates of SVR24 and ALT normalization vs BLV or PegIFN monotherapy. Combination therapy was well tolerated with AEs, which was consistent with PegIFN monotherapy.

Analogic (United States) (US), Carol Davila University of Medicine and Pharmacy (RO), Sechenov University (RU), University of Milan (IT), Université Paris Cité (FR), Hôpital Beaujon (FR), Centre Hospitalier Universitaire de Grenoble (FR), Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico (IT), Medizinische Hochschule Hannover (DE), Sorbonne Université (FR), Ospedale Maggiore (IT), Hôpital de la Croix-Rousse (FR), Hôpital Cochin (FR), Ural State Medical University (RU), Assistance Publique – Hôpitaux de Paris (FR), Research Institute of Emergency Care (RU), Institutul National Victor Babes (RO), Hôpital Saint Joseph (FR), Pitié-Salpêtrière Hospital (FR), Moscow Institute of Modern Business (RU), Infectious Clinical Hospital No. 1 (RU), Spitalul Clinic Dr. Victor Babes (RO), Gilead Sciences (United States) (US), Istituti di Ricovero e Cura a Carattere Scientifico (IT)
Good health and well-being
Openalex Percentile: Top 78%
Hepatitis C virus research
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