Improvement in 3 noninvasive tests through 144 weeks of bulevirtide monotherapy in patients with chronic hepatitis Delta with and without virologic response

Introduction: Bulevirtide (BLV) is a therapy for patients (pts) with chronic hepatitis delta (CHD); noninvasive tests (NITs) have shown improvements in hepatic function and liver disease burden with BLV treatment.

Objective: To assess changes in NITs through 3 years of BLV treatment.

Methodology: A longitudinal analysis was conducted using the Phase 3 MYR301 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). Pts with CHD (n=150) were randomised to either no treatment for 48W 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). Pts with HDV RNA values missing at W144 were excluded. Results are reported as median (quartile [Q]1, Q3).

Results: Overall, 149 pts 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 (Table 1). 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 (Table 2). Similar patterns of improvement were seen in ALT levels and APRI scores ([Fig. 1] [2]).

Fig. 1  

Fig. 2  

Conclusion: Treatment with BLV monotherapy for up to 3 years improved NIT markers in pts with CHD and were greater with longer treatment duration. These improvements were seen even among the pts without viral response.

 

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Publication History

Article published online:
04 September 2025