Study to Assess Efficacy and Safety of Bulevirtide in Participants With Chronic Hepatitis Delta (CHD)

Summary

The primary objective of this study is to evaluate the efficacy of bulevirtide administered subcutaneously (SC) for 48 weeks at a dose of 2 mg or 10 mg once daily for treatment of chronic hepatitis delta (CHD) in comparison to delayed treatment. The main goal of this study is to determine the effectiveness of bulevirtide in participants randomized to bulevirtide 2 mg or 10 mg once daily SC as compared to participants randomized to delayed treatment for 48 weeks. Treatment will continue through Week 144 (participants randomized to delayed treatment will change to bulevirtide 10 mg once daily SC after Week 48 through Week 144). All participants will be followed off-treatment for an additional 96 weeks.

Timeline

Start

2019-04-17

Primary completion

2020-11-26

Completion

2024-08-08

Outcome

Met primary endpoint

registry Delayed Treatment vs Bulevirtide 10 mg/Day; p <0.0001; Difference in percentages 46.0 (96% CI 30.5 to 61.4) NCT03852719 ↗

registry Delayed Treatment vs Bulevirtide 2 mg/Day; p <0.0001; Difference in percentages 42.9 (96% CI 27.0 to 58.5) NCT03852719 ↗

Publications

• Background Wedemeyer H, Aleman S, Andreone P, Blank A, Brunetto M, Bogomolov P, et al. Bulevirtide Monotherapy at Low and High Doses in Patients With Chronic Hepatitis Delta: 24 Weeks Interim Data of the Phase 3 MYR301 Study [Poster 2730]. European Association for the Study of the Liver (EASL): The Digital International Liver Congress; 2021 23-26 June.
• Background Wedemeyer H, Aleman S, Brunetto M, Blank A, Andreone P, Bogomolov P, et al. Efficacy and Safety of Bulevirtide Monotherapy Given at 2 mg or 10 mg Dose Level Once Daily for Treatment of Chronic Hepatitis Delta: Week 48 Primary Endpoint Results From a Phase 3 Randomized, Multicenter, Parallel Design Study [Oral Presentation 509]. EASL The International Liver Congress; 2022 22-26 June; London, UK.
• Background Lampertico P, Roulot D, Wedemeyer H. Bulevirtide with or without pegIFNalpha for patients with compensated chronic hepatitis delta: From clinical trials to real-world studies. J Hepatol. 2022 Nov;77(5):1422-1430. doi: 10.1016/j.jhep.2022.06.010. Epub 2022 Jun 22.
• Background Wedemeyer H, Aleman S, Brunetto M, Blank A, Andreone P, Bogomolov P, et al. Efficacy and Safety at 96 weeks of Bulevirtide 2 mg or 10 mg Monotherapy for Chronic Hepatitis D: Results From an Interim Analysis of a Phase 3 Randomized Study. [Oral Presentation OS-068]. EASL The International Liver Congress; 2023 21-24 June; Vienna, AUS.
• Background Wedemeyer H, Aleman S, Brunetto MR, Blank A, Andreone P, Bogomolov P, Chulanov V, Mamonova N, Geyvandova N, Morozov V, Sagalova O, Stepanova T, Berger A, Manuilov D, Suri V, An Q, Da B, Flaherty J, Osinusi A, Liu Y, Merle U, Schulze Zur Wiesch J, Zeuzem S, Ciesek S, Cornberg M, Lampertico P; MYR 301 Study Group. A Phase 3, Randomized Trial of Bulevirtide in Chronic Hepatitis D. N Engl J Med. 2023 Jul 6;389(1):22-32. doi: 10.1056/NEJMoa2213429. Epub 2023 Jun 22.
• Background Wedemeyer H, Aleman S, Brunetto M, Blank A, Andreone P, Bogomolov P, Chulanov V, Mamonova N, Geyvandova N, Morozov V, Sagalova O, Stepanova T, Berger A, Ciesek S, Manuilov D, Mercier RC, Da BL, Chee GM, Li M, Flaherty JF, Lau AH, Osinusi A, Schulze Zur Wiesch J, Cornberg M, Zeuzem S, Lampertico P. Bulevirtide monotherapy in patients with chronic HDV: Efficacy and safety results through week 96 from a phase III randomized trial. J Hepatol. 2024 Oct;81(4):621-629. doi: 10.1016/j.jhep.2024.05.001. Epub 2024 May 9.
• Background Aleman S, Brunetto M, Blank A et al. Efficacy and Safety of Bulevirtide Monotherapy for Chronic Hepatitis Delta: Posttreatment Results Through 48 Weeks After the End of Treatment From an Interim Analysis of a Randomized Phase 3 Study, MYR301; The Liver Meeting, American Association for the Study of Liver Diseases; 2024 15-19 November; San Diego, USA.
• Background Wedemeyer H, Aleman S, Blank A et al. Final results of MYR301: A Randomised Phase 3 Study Evaluating the Efficacy and Safety of up to 144 Weeks of Bulevirtide Monotherapy For Chronic Hepatitis Delta and 96 Weeks of Posttreatment Follow-up. EASL The International Liver Congress; 2025 7-10 May, Amsterdam, Netherlands.
• Wedemeyer H, Aleman S, Blank A, Andreone P, Bogomolov P, Chulanov V, Mamonova N, Geyvandova N, Morozov V, Sagalova O, Stepanova T, Berger A, Ciesek S, Lichtman A, Manuilov D, Mercier RC, Arterburn S, Christian-Cox F, Tseng S, Osinusi A, Schulze Zur Wiesch J, Cornberg M, Zeuzem S, Brunetto MR, Lampertico P. 144 Weeks of bulevirtide monotherapy for chronic hepatitis D: Final and posttreatment results from a Phase 3 randomized trial. J Hepatol. 2026 Apr 9:S0168-8278(26)00201-1. doi: 10.1016/j.jhep.2026.03.046. Online ahead of print.
• Wong RJ, Gish RG, Jacobson IM, Lim JK, Rock M, Kinyik-Merena C, Ma H, Smith N, Kim C. Impact of Double Reflex Testing and Linkage to Treatment on Clinical Outcomes of Chronic Hepatitis Delta Virus Infection in the United States. J Viral Hepat. 2026 Jan;33(1):e70119. doi: 10.1111/jvh.70119.
• Asselah T, Lampertico P, Aleman S, Bourliere M, Streinu-Cercel A, Bogomolov P, Morozov V, Stepanova T, Lazar S, Manuilov D, Mercier RC, Tseng S, Ye L, Flaherty JF, Osinusi A, Da BL, Chee GM, Lau AH, Brunetto MR, Wedemeyer H. Bulevirtide Monotherapy Is Safe and Well Tolerated in Chronic Hepatitis Delta: An Integrated Safety Analysis of Bulevirtide Clinical Trials at Week 48. Liver Int. 2025 Apr;45(4):e16174. doi: 10.1111/liv.16174. Epub 2024 Dec 8.
• Buti M, Wedemeyer H, Aleman S, Chulanov V, Morozov V, Sagalova O, Stepanova T, Gish RG, Lloyd A, Kaushik AM, Suri V, Manuilov D, Osinusi AO, Flaherty JF, Lampertico P. Patient-reported outcomes in chronic hepatitis delta: An exploratory analysis of the phase III MYR301 trial of bulevirtide. J Hepatol. 2025 Jan;82(1):28-36. doi: 10.1016/j.jhep.2024.06.031. Epub 2024 Jul 14.
• Allweiss L, Volmari A, Suri V, Wallin JJ, Flaherty JF, Manuilov D, Downie B, Lutgehetmann M, Bockmann JH, Urban S, Wedemeyer H, Dandri M. Blocking viral entry with bulevirtide reduces the number of HDV-infected hepatocytes in human liver biopsies. J Hepatol. 2024 Jun;80(6):882-891. doi: 10.1016/j.jhep.2024.01.035. Epub 2024 Feb 8.
• Hollnberger J, Liu Y, Xu S, Chang S, Martin R, Manhas S, Aeschbacher T, Han B, Yazdi T, May L, Han D, Shornikov A, Flaherty J, Manuilov D, Suri V, Asselah T, Lampertico P, Wedemeyer H, Aleman S, Richards C, Mateo R, Maiorova E, Cihlar T, Mo H, Urban S. No virologic resistance to bulevirtide monotherapy detected in patients through 24 weeks treatment in phase II and III clinical trials for chronic hepatitis delta. J Hepatol. 2023 Sep;79(3):657-665. doi: 10.1016/j.jhep.2023.04.027. Epub 2023 Apr 27.

Drugs

Evaluation	Drug	Modality	Dose	Route
Subject	Bulevirtide	Protein / enzyme biologic	2 mg	Subcutaneous
Subject	Bulevirtide	Protein / enzyme biologic	10 mg	Subcutaneous

Indications