Improvement in 3 Noninvasive Tests Through 144 Weeks of Bulevirtide Monotherapy in Patients with Chronic Hepatitis Delta with and Without Virologic Response

Bulevirtide (BLV) is an entry inhibitor approved in Europe and Australia as a therapy for patients with chronic hepatitis delta (CHD); noninvasive tests (NITs) have demonstrated improvements in hepatic function and burden of liver disease with BLV treatment. Here we describe changes in NITs through up to 3 years of treatment.A longitudinal analysis was conducted using the Phase 3 MYR301 (NCT03852719) study data to determine the effect of BLV on results of alanine aminotransferase (ALT) level measurements and 3 NITs: fibrosis index based on 4 factors (FIB-4), aspartate aminotransferase to platelet ratio index (APRI), and liver stiffness measurement (LSM). In total, 150 patients with CHD were randomised to either no treatment for 48 weeks (W) followed by BLV 10 mg/d for 96W, or to BLV 2 or 10 mg/d for 144W. Change from baseline (BL) in NITs was assessed through 96W and 144W of treatment. This analysis was repeated for the pooled immediate treatment groups stratified by hepatitis delta virus (HDV) RNA response at W144: virologic responders (VR; undetectable HDV RNA or ≥ 2 log10 IU/mL decline in HDV RNA from BL), partial responders (PR; ≥ 1 log10 IU/mL but < 2 log10 IU/mL decline in HDV RNA from BL), and nonresponders (NR; < 1 log10 IU/mL decline in HDV RNA from BL). Patients with HDV RNA values missing at W144 were excluded. Results are reported as median (quartile [Q]1, Q3) unless otherwise stated.Overall, 149 patients with CHD were treated with BLV monotherapy (BLV 2 mg [n = 49]; BLV 10 mg [n = 100]); 99 were randomised to immediate BLV treatment for 144W, and 50 in the BLV 10 mg group received treatment for 96W. NITs showed improvements in all cohorts after 48W of therapy, which were maintained through 144W of therapy. Changes from BL at W144 were: BLV 2 mg group, FIB-4, −0.52 (−1.19, −0.03); LSM, −4.00 (−6.00, −1.00) kPa; immediate BLV 10 mg treatment group, FIB-4, −0.43 (−0.94, −0.14); LSM, −3.80 (−6.70, −1.20) kPa; and BLV delayed treatment group at W144 after 96W of treatment, FIB-4, −0.27 (−0.62, 0.02); LSM, −3.15 (−7.00, −0.40) kPa. Improvements at W144 in NITs were also seen across all viral response groups in the pooled immediate treatment cohort, including VR (n = 74), PR (n = 7), and NR (n = 8) at W144. Among VR, changes from BL were FIB-4, −0.43 (−1.05, −0.11); and LSM, −3.85 (−6.50, −1.20) kPa. Among PR, changes from BL were FIB-4, −0.39 (−0.48, −0.09); and LSM, −1.30 (−3.80, 0.20) kPa. Among NR, changes from BL were FIB-4, −1.02 (−1.60, −0.78); and LSM, −4.00 (−15.70, −1.10) kPa. Changes from BL in ALT levels and APRI scores were consistent with the trends observed in FIB-4 across all treatment cohorts. Treatment with BLV 2 or 10 mg monotherapy for up to 3 years resulted in longitudinal improvements in NITs in patients with CHD and were numerically greater with longer treatment duration. These improvements were seen even among the few patients without viral response.