P3779 - Final Results of MYR301: A Randomized Phase 3 Study Evaluating the Efficacy and Safety of Up to 144 Weeks of Bulevirtide Monotherapy for Chronic Hepatitis Delta and 96 Weeks of Post-Treatment Follow-Up

Heiner Wedemeyer, MD¹, Soo Aleman, MD, PhD², Antje Blank, MD³, Pietro Andreone, MD⁴, Pavel Bogomolov, MD, PhD⁵, Vladimir Chulanov, MD, PhD, DSc⁶, Nina Mamonova, MD⁷, Natalia Geyvandova, MD⁸, Viacheslav Morozov, MD, PhD⁹, Olga Sagalova, PhD¹⁰, Tatiana Stepanova, MD¹¹, Annemarie Berger, MD¹², Sandra Ciesek, MD, PhD¹², Amos Lichtman, MD, MPH¹³, Dmitry Manuilov, MD¹³, Renee-Claude Mercier, PharmD¹³, Sarah Arterburn, MS¹³, Florence Christian-Cox, BSc¹³, Steve Tseng, MD¹³, Anu Osinusi, MD, MPH¹³, Julian Schulze zur Wiesch, MD¹⁴, Markus Cornberg, MD¹, Stefan Zeuzem, MD¹⁵, Maurizia R. Brunetto, MD¹⁶, Pietro Lampertico, MD, PhD¹⁷
1Clinic for Gastroenterology, Hepatology, Infectious Diseases, and Endocrinology, Hannover Medical School, Hannover, Sachsen, Germany; 2Department of Infectious Diseases, Karolinska University Hospital/Karolinska Institutet, Stockholm, Stockholms Lan, Sweden; 3Medical Faculty Heidelberg/Heidelberg University Hospital, Department of Clinical Pharmacology and Pharmacoepidemiology, Heidelberg, Baden-Wurttemberg, Germany; 4Department of Internal Medicine, Baggiovara Hospital, University of Modena and Reggio Emilia, Modena, Italy, Modena, Emilia-Romagna, Italy; 5M.F. Vladimirsky Moscow Regional Research and Clinical Institute, Moscow, Moskva, Russia; 6Sechenov University, Moscow, Moskva, Russia; 7FSBI National Research Medical Center for Phthisiopulmonology and Infectious Diseases of the Ministry of Health of the Russian Federation, Moscow, Moskva, Russia; 8Stavropol Regional Hospital, Stavropol, Stavropol', Russia; 9LLC Medical Company “Hepatolog”, Samara, Samara, Russia; 10South Ural State Medical University, Chelyabinsk, Orel, Russia; 11LLC Clinic of Modern Medicine, Moscow, Moskva, Russia; 12External partner site Frankfurt, German Center for Infection Research (DZIF), Institute for Medical Virology, University Hospital Frankfurt, Goethe University Frankfurt, Frankfurt, Hessen, Germany; 13Gilead Sciences, Inc., Foster City, CA; 14Hepatology Outpatient Medical Clinic, University Hospital Hamburg-Eppendorf, Hamburg, Hamburg, Germany; 15Department of Medicine, University Hospital, Goethe University Frankfurt, Frankfurt, Hessen, Germany; 16Hepatology Unit, Reference Center of the Tuscany Region for Chronic Liver Disease and Cancer, University Hospital of Pisa; Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Toscana, Italy; 17Division of Gastroenterology and Hepatology, Foundation IRCCS Ca’ Granda Ospedale Maggiore Policlinico; CRC “A. M. and A. Migliavacca” Center for Liver Disease, Department of Pathophysiology and Transplantation, University of Milan, Milan, Lombardia, Italy

Introduction: Bulevirtide (BLV) 2 mg/day (d) is approved in Europe, Australia, and Russia for treatment of compensated chronic hepatitis delta (CHD). In MYR301, a Phase 3 study evaluating BLV monotherapy for 2–3 years, BLV was safe and effective through 144 weeks (W). We present final MYR301 results through follow-up at 96W posttreatment (FU96).

Methods: Patients (pts) with compensated CHD (N = 150) were randomized to immediate treatment with BLV 2 or 10 mg/d for 144W or to 48W of delayed treatment (DT) followed by BLV 10 mg/d for 96W (DT to 10 mg) and FU96. Efficacy endpoints included virologic response (VR; undetectable hepatitis delta virus [HDV] RNA or ≥2 log₁₀ IU/mL decline from baseline), combined response (CR; VR and alanine aminotransferase [ALT] normalization), ALT normalization, undetectable HDV RNA, and hepatitis B surface antigen (HBsAg) loss. The primary analysis was intention to treat with missing data considered failures.

Results: Most patients (92%) remained in the study at the end of treatment (EOT); 72% and 57% completed FU48 and FU96, respectively. CR rates in the 2, 10, and DT to 10 mg groups, respectively, declined from 57%, 54%, and 56% at EOT to 24% in each group at FU96. HDV RNA undetectability rates were 29%, 50%, and 52% at EOT and 20%, 22%, and 20% at FU96. Of the 64 pts with undetectable HDV RNA at EOT and FU data, 23 (36%) had sustained undetectable HDV RNA through FU96, and 41 pts had viral relapse, which occurred in 38 (93%) by FU24 and none after FU48. Sustained posttreatment HDV RNA undetectability was more frequent in pts with longer on-treatment continuous undetectability at EOT: 9/10 (90%) for ≥96W, 11/22 (50%) for ≥48W to < 96W, and 3/32 (9%) for 0W to < 48W. Posttreatment HBsAg loss occurred in 3 pts. In the posttreatment period, 14/142 (10%) pts had ALT >10 × the upper limit of normal (ULN), which occurred by FU24 in most (10/14, 71%). Posttreatment hepatic serious adverse events (SAEs) were reported in 20/142 (14%) pts: 7, ALT >10 × ULN; 4, liver-related hospitalization; 1, nonserious ascites. The hepatic SAEs resolved in 17/20 (85%) pts, ≥16 of whom restarted BLV.

Discussion: In pts with CHD treated with BLV monotherapy for 96W or 144W, response rates decreased after treatment discontinuation. Some pts maintained undetectable HDV RNA for 2 years posttreatment. Only in the first year after EOT was posttreatment viral relapse observed, which may be associated with hepatitis flares. HW and SAleman contributed equally; MRB and PL contributed equally.

Disclosures:
Heiner Wedemeyer: Abbott Laboratories – Advisory Committee/Board Member, Consultant, Grant/Research Support, Speakers Bureau. Abbott Molecular – Advisory Committee/Board Member, Consultant, Grant/Research Support, Speakers Bureau. Albireo Pharma – Advisory Committee/Board Member, Consultant, Speakers Bureau. AstraZeneca – Advisory Committee/Board Member, Consultant, Speakers Bureau. Atea Pharmaceuticals – Advisory Committee/Board Member, Consultant, Speakers Bureau. BioMarin Pharmaceutical – Advisory Committee/Board Member, Consultant, Speakers Bureau. Biotest – Advisory Committee/Board Member, Consultant, Grant/Research Support, Speakers Bureau. Bristol Myers Squibb – Advisory Committee/Board Member, Consultant, Speakers Bureau. CSL Behring – Advisory Committee/Board Member, Consultant, Speakers Bureau. Dr. Falk Pharma – Advisory Committee/Board Member, Consultant, Speakers Bureau. Falk Foundation – Advisory Committee/Board Member, Consultant, Speakers Bureau. Gilead Sciences, Inc. – Advisory Committee/Board Member, Consultant, Speakers Bureau. GSK – Advisory Committee/Board Member, Consultant, Speakers Bureau. Janssen – Advisory Committee/Board Member, Consultant, Speakers Bureau. Lilly Deutschland – Advisory Committee/Board Member, Consultant, Speakers Bureau. Merck Sharp & Dohme – Advisory Committee/Board Member, Consultant, Speakers Bureau. Mirum Pharma Germany – Advisory Committee/Board Member, Consultant, Speakers Bureau. Olink – Advisory Committee/Board Member, Consultant, Speakers Bureau. Orphalan – Advisory Committee/Board Member, Consultant, Speakers Bureau. Pfizer – Advisory Committee/Board Member, Consultant, Speakers Bureau. Roche – Advisory Committee/Board Member, Consultant, Speakers Bureau. Roche Diagnostics International – Advisory Committee/Board Member, Consultant, Speakers Bureau. Roche Pharma – Advisory Committee/Board Member, Consultant, Speakers Bureau. Swedish Orphan Biovitrum – Advisory Committee/Board Member, Consultant, Speakers Bureau. Takeda Pharma Vertrieb – Advisory Committee/Board Member, Consultant, Speakers Bureau. Vir Biotechnology – Advisory Committee/Board Member, Consultant, Speakers Bureau.
Soo Aleman: AbbVie – Honoraria for educational events, Speakers Bureau. Biogen – Honoraria for educational events, Speakers Bureau. Gilead Sciences, Inc. – Honoraria for educational events, Speakers Bureau. GSK – Honoraria for educational events, Speakers Bureau. Janssen – Honoraria for educational events, Speakers Bureau. Merck Sharp & Dohme – Honoraria for educational events, Speakers Bureau. MYR GmbH – Honoraria for educational events, Speakers Bureau. Roche – Honoraria for educational events, Speakers Bureau. Spring Bank Pharmaceuticals – Honoraria for educational events, Speakers Bureau.
Antje Blank: Gilead Sciences, Inc. – Research funding. MYR GmbH – Research funding.
Pietro Andreone indicated no relevant financial relationships.
Pavel Bogomolov: AbbVie – Grant/Research Support, Speakers Bureau. Bayer – Grant/Research Support, Speakers Bureau. Gilead Sciences, Inc. – Grant/Research Support, Speakers Bureau. Hepatera – Grant/Research Support, Speakers Bureau. Merck Sharp & Dohme – Grant/Research Support, Speakers Bureau. Norvo Nordisk – Grant/Research Support, Speakers Bureau. R-Pharm – Grant/Research Support, Speakers Bureau.
Vladimir Chulanov: AbbVie – Consultant, Speakers Bureau. AstraZeneca – Consultant, Speakers Bureau. Bristol Myers Squibb – Consultant, Speakers Bureau. Gilead Sciences, Inc. – Consultant, Speakers Bureau. GSK – Consultant, Speakers Bureau. Hepatera – Consultant, Speakers Bureau. Merck Sharp & Dohme – Consultant, Speakers Bureau. Roche – Consultant, Speakers Bureau. R-Pharm – Consultant, Speakers Bureau.
Nina Mamonova indicated no relevant financial relationships.
Natalia Geyvandova indicated no relevant financial relationships.
Viacheslav Morozov indicated no relevant financial relationships.
Olga Sagalova indicated no relevant financial relationships.
Tatiana Stepanova indicated no relevant financial relationships.
Annemarie Berger indicated no relevant financial relationships.
Sandra Ciesek indicated no relevant financial relationships.
Amos Lichtman: Gilead Sciences, Inc. – Employee, Stock Options.
Dmitry Manuilov: Gilead Sciences, Inc. – Employee, Stock Options.
Renee-Claude Mercier: Gilead Sciences, Inc. – Employee, Stock Options.
Sarah Arterburn: Gilead Sciences, Inc. – Employee, Stock Options.
Florence Christian-Cox: Gilead Sciences, Inc. – Employee, Stock Options.
Steve Tseng: Gilead Sciences, Inc. – Employee, Stock Options.
Anu Osinusi: Gilead Sciences, Inc. – Employee, Stock Options.
Julian Schulze zur Wiesch: Gilead Sciences, Inc. – Consultant.
Markus Cornberg: AbbVie – Honoraria. Falk – Honoraria. Gilead Sciences, Inc. – Honoraria. GSK – Honoraria. Janssen-Cilag – Honoraria. Merck Sharp & Dohme – Honoraria. Novartis – Honoraria. Roche – Honoraria. Spring Bank Pharmaceuticals – Honoraria. Swedish Orphan Biovitrum – Honoraria.
Stefan Zeuzem indicated no relevant financial relationships.
Maurizia Brunetto: AbbVie – Consultant, Speakers Bureau. AstraZeneca – Consultant, Speakers Bureau. Gilead Sciences, Inc. – Consultant, Speakers Bureau. Janssen – Consultant, Speakers Bureau. Merck Sharp & Dohme-Eisai – Consultant, Speakers Bureau. Roche – Consultant, Speakers Bureau.
Pietro Lampertico: AbbVie – Advisory Committee/Board Member, Speakers Bureau. Aligos Therapeutics – Advisory Committee/Board Member, Speakers Bureau. Alnylam Pharmaceuticals – Advisory Committee/Board Member, Speakers Bureau. Antios Therapeutics – Advisory Committee/Board Member, Speakers Bureau. Arrowhead Pharmaceuticals – Advisory Committee/Board Member, Speakers Bureau. Bristol Myers Squibb – Advisory Committee/Board Member, Speakers Bureau. Eiger Pharmaceuticals – Advisory Committee/Board Member, Speakers Bureau. Gilead Sciences, Inc. – Advisory Committee/Board Member, Speakers Bureau. GSK – Advisory Committee/Board Member, Speakers Bureau. Janssen – Advisory Committee/Board Member, Speakers Bureau. Merck Sharp & Dohme – Advisory Committee/Board Member, Speakers Bureau. MYR GmbH – Advisory Committee/Board Member, Speakers Bureau. Roche – Advisory Committee/Board Member, Speakers Bureau. Spring Bank Pharmaceuticals – Advisory Committee/Board Member, Speakers Bureau.

Heiner Wedemeyer, MD¹, Soo Aleman, MD, PhD², Antje Blank, MD³, Pietro Andreone, MD⁴, Pavel Bogomolov, MD, PhD⁵, Vladimir Chulanov, MD, PhD, DSc⁶, Nina Mamonova, MD⁷, Natalia Geyvandova, MD⁸, Viacheslav Morozov, MD, PhD⁹, Olga Sagalova, PhD¹⁰, Tatiana Stepanova, MD¹¹, Annemarie Berger, MD¹², Sandra Ciesek, MD, PhD¹², Amos Lichtman, MD, MPH¹³, Dmitry Manuilov, MD¹³, Renee-Claude Mercier, PharmD¹³, Sarah Arterburn, MS¹³, Florence Christian-Cox, BSc¹³, Steve Tseng, MD¹³, Anu Osinusi, MD, MPH¹³, Julian Schulze zur Wiesch, MD¹⁴, Markus Cornberg, MD¹, Stefan Zeuzem, MD¹⁵, Maurizia R. Brunetto, MD¹⁶, Pietro Lampertico, MD, PhD¹⁷. P3779 - Final Results of MYR301: A Randomized Phase 3 Study Evaluating the Efficacy and Safety of Up to 144 Weeks of Bulevirtide Monotherapy for Chronic Hepatitis Delta and 96 Weeks of Post-Treatment Follow-Up, ACG 2025 Annual Scientific Meeting Abstracts. Phoenix, AZ: American College of Gastroenterology.