P4566 - Efficacy and Safety of Bulevirtide Monotherapy for Chronic Hepatitis Delta in Patients With and Without Cirrhosis: Results From the Week 96 Interim Analysis of a Phase 3 Randomized Study

Award: Presidential Poster Award

Soo Aleman, MD, PhD¹, Heiner Wedemeyer, MD², Maurizia Brunetto, MD³, Antje Blank, MD⁴, Pietro Andreone, MD⁵, Pavel Bogomolov, PhD⁶, Vladimir Chulanov, MD, PhD⁷, Nina Mamonova, PhD⁷, Natalia Geyvandova, MD, PhD⁸, Viacheslav Morozov, PhD⁹, Olga Sagalova, PhD¹⁰, Tatyana Stepanova, PhD¹¹, Dmitry Manuilov, MD¹², Renee-Claude Mercier, PharmD¹², Qi An, PhD¹², Ben Da, MD¹², John F. Flaherty, PharmD¹², Paul Buensuceso, MD¹², Anu Osinusi, MD, MPH¹², Audrey H. Lau, MD, PhD¹², Florence Christian-Cox, BSc¹², Steve Tseng, MD¹², Julian Schulze zur Wiesch, MD¹³, Markus Cornberg, MD¹⁴, Stefan Zeuzem, MD¹⁵, Pietro Lampertico, MD, PhD^16
1Karolinska University Hospital, Karolinska Institutet, Stockholm, Stockholms Lan, Sweden; ²Hannover Medical School, Hannover, Niedersachsen, Germany; ³University Hospital, Pisa, Toscana, Italy; ⁴Heidelberg University Hospital, Heidelberg, Baden-Wurttemberg, Germany; ⁵University of Modena and Reggio Emilia, Modena, Emilia-Romagna, Italy; ⁶State Budgetary Institution of Health Care of Moscow Region, Moscow Regional Research Clinical Institute After M.F. Vladimirsky, 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 of Ministry of Health of the Russian Federation, Chelyabinsk, Sverdlovsk, Russia; ¹¹Limited liability company “Clinic of Modern Medicine”, Moscow, Moskva, Russia; ¹²Gilead Sciences, Inc., Foster City, CA; ¹³Universitätsklinikum Hamburg-Eppendorf, Hamburg, Hamburg, Germany; ¹⁴Medizinische Hochschule Hannover, Hannover, Nordrhein-Westfalen, Germany; ¹⁵University Hospital Frankfurt, Frankfurt, Hessen, Germany; ¹⁶Foundation IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Lombardia, Italy

Introduction: Bulevirtide (BLV) is a first-in-class entry inhibitor for chronic hepatitis delta (CHD) approved in the EU. Results from an interim Week 96 analysis for MYR301, a Phase 3 study, showed improved efficacy and continued favorable safety in patients treated with BLV 2 or 10 mg/d compared to Week 48 findings. As 47% of patients entering the trial had cirrhosis, we present here Week 96 efficacy and safety results in this patient subset with the highest risk for liver complications compared to noncirrhotics.

Methods: In MYR301 (NCT03852719), 150 patients with CHD were randomized (1:1:1) and stratified based on the presence/absence of compensated cirrhosis as follows: Arm A: no anti-HDV treatment for 48 weeks followed by BLV 10 mg/d for 96 weeks (n=51); Arms B and C: immediate treatment with BLV 2 mg/d (n=49) or 10 mg/d (n=50), respectively, for 144 weeks, with follow-up for 96 weeks after end of treatment. Combined response was defined as undetectable HDV RNA or a decrease by ≥ 2 log₁₀ IU/mL from baseline and ALT normalization; other endpoints included viral response, biochemical response, log₁₀ change in HDV RNA, and HBsAg.

Results: Baseline characteristics were similar between arms: mean (SD) age 41.8 (8.4) years, 57% males, 83% White, mean (SD) HDV RNA 5.0 (1.3) log₁₀ IU/mL, mean (SD) ALT 111 (69) U/L, mean (SD) liver stiffness 15 (8.8) kPa, and 61% were on concomitant nucleos(t)ide analogue therapy. Of 150 patients, 71 (47%) had cirrhosis at baseline, while 79 (53%) were considered noncirrhotic (Table). Overall efficacy responses at Week 96 were similar among patients with and without cirrhosis for BLV 2 and 10 mg. Numerically higher rates of viral responses were observed among those with cirrhosis, while numerically higher rates of ALT normalization were seen in noncirrhotics. Comparable declines in HDV RNA and ALT levels were seen in patients with and without cirrhosis. Undetectable HDV RNA was achieved by 38% (18/47) of those with cirrhosis treated with BLV 2 or 10 mg for 96 weeks. Bile acid changes from baseline were similar between patients with and without cirrhosis through Week 96. BLV was safe and well tolerated in both patients with and without cirrhosis; there were no drug discontinuations, SAEs, or deaths attributed to BLV.

Discussion: BLV as a monotherapy for CHD through Week 96 was efficacious and safe in patients with and without cirrhosis. Consistent HDV RNA and ALT level declines were seen regardless of cirrhosis status.


Disclosures:


Soo Aleman, MD, PhD¹, Heiner Wedemeyer, MD², Maurizia Brunetto, MD³, Antje Blank, MD⁴, Pietro Andreone, MD⁵, Pavel Bogomolov, PhD⁶, Vladimir Chulanov, MD, PhD⁷, Nina Mamonova, PhD⁷, Natalia Geyvandova, MD, PhD⁸, Viacheslav Morozov, PhD⁹, Olga Sagalova, PhD¹⁰, Tatyana Stepanova, PhD¹¹, Dmitry Manuilov, MD¹², Renee-Claude Mercier, PharmD¹², Qi An, PhD¹², Ben Da, MD¹², John F. Flaherty, PharmD¹², Paul Buensuceso, MD¹², Anu Osinusi, MD, MPH¹², Audrey H. Lau, MD, PhD¹², Florence Christian-Cox, BSc¹², Steve Tseng, MD¹², Julian Schulze zur Wiesch, MD¹³, Markus Cornberg, MD¹⁴, Stefan Zeuzem, MD¹⁵, Pietro Lampertico, MD, PhD¹⁶. P4566 - Efficacy and Safety of Bulevirtide Monotherapy for Chronic Hepatitis Delta in Patients With and Without Cirrhosis: Results From the Week 96 Interim Analysis of a Phase 3 Randomized Study, ACG 2024 Annual Scientific Meeting Abstracts. Philadelphia, PA: American College of Gastroenterology.