A0467 - Bulevirtide Monotherapy at Low and High Dose in Patients With Chronic Hepatitis Delta: 24-Week Interim Data of the Phase 3 MYR301 Study

Stacey Lee, DMSc, PA-C¹, Heiner Wedemeyer, MD², Soo Aleman, PhD³, Maurizia Brunetto, MD⁴, Antje Blank, MD⁵, Pietro Andreone, MD⁶, Pavel Bogomolov, PhD⁷, Vladimir Chulanov, MD, PhD⁸, Nina Mamonova, PhD⁸, Natalia Geyvandova, MD, PhD⁹, Viacheslav Morozov, PhD¹⁰, Olga Sagalova, PhD¹¹, Tatyana Stepanova, PhD¹², Dmitry Manuilov, MD¹³, Vithika Suri, PhD¹³, Qi An, PhD¹³, John F. Flaherty, PharmD¹³, Anu Osinusi, MD, MPH¹³, Julian Schulze zur Wiesch, MD¹⁴, Markus Cornberg, MD², Stefan Zeuzem, MD¹⁵, Pietro Lampertico, MD, PhD^16
1Gilead Sciences, Inc., Charlotte, NC; ²Medizinische Hochschule Hannover, Hannover, Niedersachsen, Germany; ³Karolinska University Hospital/Karolinska Institutet, Stockholm, Stockholms Lan, Sweden; ⁴University Hospital of Pisa and Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Toscana, Italy; ⁵Heidelberg University Hospital, Heidelberg, Baden-Wurttemberg, Germany; ⁶University of Modena and Reggio Emilia, Modena, Emilia-Romagna, Italy; ⁷State Budgetary Institution of Health Care of Moscow, Moscow, Moskva, Russia; ⁸FSBI National Research Medical Center for Phthisiopulmonology and Infectious Diseases of the Ministry of Health of the Russian Federation, Moscow, Moskva, Russia; ⁹Stavropol Regional Hospital, Stavropol, Stavropol', Russia; ¹⁰LLC Medical Company “Hepatolog”, Samara, Samara, Russia; ¹¹Southern Ural State Medical University of Ministry of Health of the Russian Federation, Chelyabinsk, Kurgan, Russia; ¹²LLC “Clinic of Modern Medicine”, Moscow, Moskva, Russia; ¹³Gilead Sciences, Inc., Foster City, CA; ¹⁴Universitätsklinikum Hamburg-Eppendorf Medizinische Klinik Studienambulanz Hepatologie, Hamburg, Hamburg, Germany; ¹⁵University Hospital Frankfurt, Frankfurt am Main, Hessen, Germany; ¹⁶Foundation IRCCS Ca’ Granda Ospedale Maggiore Policlinico; CRC “A. M. and A. Migliavacca” Center for Liver Disease, University of Milan, Milan, Lombardia, Italy

Introduction: Bulevirtide (BLV) is a first-in-class entry inhibitor for the treatment of chronic hepatitis D virus (cHDV) infection. BLV has shown pronounced virologic and biochemical responses in two Phase 2 trials. We present findings of a predefined 24-week interim analysis of the MYR301 Phase 3 study in HBV/HDV co-infected patients receiving 2 or 10 mg qd BLV monotherapy in comparison to no antiviral treatment.

Methods: 150 patients with cHDV infection were randomized 1:1:1 to no antiviral treatment for 48 weeks followed by 10 mg qd BLV for 96 weeks (arm A, n=51) or to 2 mg qd BLV (arm B, n=49) or 10 mg qd BLV (arm C, n=50) for 144 weeks with a 96-week treatment-free follow-up. The primary endpoint, combined response, was defined as undetectable HDV RNA (< LoD) or decrease by ≥2 log₁₀ IU/mL and ALT normalization at week 48; secondary endpoints included undetectable HDV RNA, decline by ≥2 log₁₀ IU/mL, ALT normalization, and HBsAg decline by ≥1 log₁₀ IU/mL.

Results: Owing to a communications embargo, Week 48 data were not available for this submission. We will include those data for presentation of this abstract at the ACG conference.

Patient characteristics: 57% were male, 83% were white, mean age was 42 years. Baseline HDV RNA levels were 5.05 log₁₀ IU/mL; mean ALT was 110.9 U/L. BLV was well tolerated over the first 24 weeks; 421 treatment-emergent adverse events (TEAE) were reported: 55 TEAEs in 26 patients in arm A, 121 TEAEs in 32 patients in arm B, and 245 TEAEs in 36 patients in arm C. 48 TEAEs in arm B and 100 in arm C were assessed as possibly related to BLV. One serious TEAE was reported in one patient in arm A. At week 24, the proportions of patients achieving combined virologic and biochemical response were 37% in arm B and 28% in arm C (vs 0% in arm A, p< 0.0001). An HDV RNA decrease by ≥2 log₁₀ IU/mL at week 24 from baseline was observed in 55% of patients in arm B and 68% in arm C (vs 4% in arm A, p< 0.0001). At week 24, ALT normalization was reached by 53% of arm B and 38% of arm C (vs 6% of arm A, p< 0.0001). One patient treated with 2 mg BLV achieved an HBsAg reduction ≥1 log₁₀ IU/mL at week 24.

Discussion: This Phase 3 trial confirms that monotherapy with BLV is safe and well tolerated in patients with compensated cHDV infection. 24 weeks of treatment with BLV was associated with significant HDV RNA declines and improvements in biochemical disease activity. These findings further support the conditional approval of BLV.

Wedemeyer H et al. J Hepatol. 2021;75(2):S294-5.


Disclosures:


Stacey Lee, DMSc, PA-C¹, Heiner Wedemeyer, MD², Soo Aleman, PhD³, Maurizia Brunetto, MD⁴, Antje Blank, MD⁵, Pietro Andreone, MD⁶, Pavel Bogomolov, PhD⁷, Vladimir Chulanov, MD, PhD⁸, Nina Mamonova, PhD⁸, Natalia Geyvandova, MD, PhD⁹, Viacheslav Morozov, PhD¹⁰, Olga Sagalova, PhD¹¹, Tatyana Stepanova, PhD¹², Dmitry Manuilov, MD¹³, Vithika Suri, PhD¹³, Qi An, PhD¹³, John F. Flaherty, PharmD¹³, Anu Osinusi, MD, MPH¹³, Julian Schulze zur Wiesch, MD¹⁴, Markus Cornberg, MD², Stefan Zeuzem, MD¹⁵, Pietro Lampertico, MD, PhD¹⁶. A0467 - Bulevirtide Monotherapy at Low and High Dose in Patients With Chronic Hepatitis Delta: 24-Week Interim Data of the Phase 3 MYR301 Study, ACG 2022 Annual Scientific Meeting Abstracts. Charlotte, NC: American College of Gastroenterology.