021: Efficacy of Bulevirtide as Monotherapy for Chronic Hepatitis D (CHD): Week 48 Results from an Integrated Analysis

Statement of Purpose: Bulevirtide (BLV) is a novel first-in-class entry inhibitor for the treatment of chronic HDV infection (CHD) that was conditionally approved in the EU in July 2020. Patients treated with BLV alone have previously shown pronounced viral and biochemical responses (HDV RNA and ALT declines) through 48 weeks in a Phase 2 study (MYR203) and 24 weeks in a Phase 3 study (MYR301). Here, we present an integrated efficacy analysis of 48-week efficacy derived from these studies.

Description of Methods & Materials: A total of 180 patients with CHD without cirrhosis or with compensated cirrhosis were included in a pooled analysis including 64 and 65 patients treated with BLV at 2 mg or 10 mg given s.c. once daily, respectively, compared to 51 patients receiving no active anti-HDV treatment (control) during the 48-week analysis period. The primary efficacy endpoint was the combined response of undetectable HDV RNA or decrease by ≥2 log10 IU/mL from baseline and ALT normalization; additional endpoints included viral response (undetectable HDV RNA or decline by ≥2 log10 IU/mL), ALT normalization and log10 change in HDV RNA levels.

Data & Results: At baseline, demographics of all groups were well balanced; characteristics included: mean (SD) age 41 (8.6) years, 60.0% males, 85.6% White, 41.1% with compensated cirrhosis, 97.8% with HDV genotype 1, 47.2% interferon experienced, 58.3% were receiving nucleos(t)ide analogue therapy; with mean (SD) HDV RNA of 5.1 (1.42) log10 IU/mL, ALT of 109 (70.4) U/L and liver stiffness of 14.2 (8.40) kPa. At Week 48, the combined response rate was similar in the BLV 2 mg and 10 mg groups (46.9% and 46.2%, respectively) and higher than control (2.0%). While rates of ALT normalization were similar for those treated with BLV 2 mg and 10 mg (56.3% and 52.3%, respectively), the viral response rate was numerically lower in the BLV 2 mg group than in the BLV 10 mg group (68.8% and 78.5%) with mean (SD) change from baseline in HDV RNA at Week 48 of -2.60 (1.453) and -3.29 (1.492) log10 IU/mL, respectively. Mean (SD) change from baseline in liver stiffness was comparable in BLV 2 mg and 10 mg groups: -2.6 (5.34) and -2.8 (3.94), respectively. For all efficacy endpoints, response rates were higher in the BLV groups compared to the control group. Treatment benefit was consistent across subgroups including patients with cirrhosis.

Interpretation, Conclusion or Significance: In an integrated efficacy analysis of 48-week data from 180 CHD patients, the combined response rates and other endpoints were comparable between the BLV 2 mg and BLV 10 mg groups; treatment with BLV was better than control. These results provide additional support for the use of BLV 2 mg once daily for treatment of compensated CHD.

Disclosures: Pietro Lampertico, Soo Aleman, Antje Blank, Pavel Bogomolov, Vladimir Chulanov, Nina Mamonova, Viacheslav Morozov, Olga Sagalova, Tatyana Stepanova, Vithika Suri, Dmitry Manuilov, Lei Ye, John F. Flaherty, Anu Osinusi, Markus Cornberg, Maurizia Brunetto, Heiner Wedemeyer

PL received speaking and teaching fees from and participation in advisory committees or review panels for AbbVie, Aligos, Alnylam, Antios, Arrowhead, Bristol Myers Squibb, Eiger, Gilead Sciences Inc, GSK, Janssen, MSD, MYR GmbH, Roche and Spring Bank Pharmaceuticals; SA received grant/research support from AbbVie and Gilead Sciences Inc, and speaking and teaching fees from AbbVie, Biogen, Gilead Sciences Inc and MSD; AB received research funding from Myr GMBH; VC received consultant and sponsored lecture fees from AbbVie, AstraZeneca, BMS, Gilead Sciences Inc, GSK, Hepatera, MSD, Roche and R-Pharm; MC received honoraria from AbbVie, Falk, Gilead Sciences Inc, GSK, Jansen-Cilag, MSD, Novartis, Roche, Spring Bank Pharmaceuticals, and Swedish Orphan Biovitrum; MB received speaker’s bureau fees from AbbVie, Gilead Sciences Inc and EISAI-MSD, and advisory and consultancy fees from AbbVie, Gilead Sciences Inc, Janssen and Roche. HW received grants, consulting/advisory board fees, and speaker’s bureau fees from AbbVie, Aligos, Altimmune, Biotest, BMS, BTG, Dicerna, Enanta, Gilead Sciences, Inc., Janssen, Merck/MSD, MYR GmbH, Novartis, Roche, and Vir Biotechnology; PB, NM, and VM report no COIs.