Bulevirtide in combination with pegylated interferon alfa-2a shows a sustained off-treatment response in the liver

Background: Bulevirtide (BLV) is a first-in-class entry inhibitor approved for chronic hepatitis D (CHD). The phase-2b study MYR204 evaluated safety and efficacy of BLV with or without pegylated interferon alfa-2a (PegIFNα). This sub-study aimed to assess intrahepatic virological and host changes 24w after end of treatment (EOT).

Method: 174 CHD patients were randomized (1:2:2:2) to receive (A) PegIFNα for 48w; (B) 2mg BLV+PegIFNα or (C) 10mg BLV+PegIFNα for 48w, both followed by 48w monotherapy with BLV 2mg or 10mg, respectively; (D) 10mg BLV for 96w. Paired liver biopsies at baseline and 24w after EOT from a subset of patients were assessed by qPCR (n=42) and immunohistochemistry (n=44) for HDV, HBV and host parameters.

Results: Intrahepatic HDV-RNA levels and HDAg-positive cells decreased from baseline, with the largest reductions in the combination arms. At follow-up, 57% of patients in arm B and 73% in arm C were HDV-RNA negative. Intrahepatic changes of HDV-RNA mirrored serological HDV-RNA changes (r=0.82; p<0.0001). Intrahepatic HBV parameters did not change significantly apart from sharp declines in some patients receiving combination treatments. Decreases in infection-related genes, e.g., CXCL10, strongly correlated with the reduction of intrahepatic HDV-RNA (r=0.67; p<0.0001) and ALT levels (r=0.75; p<0.0001), suggesting ameliorated liver inflammation.

Conclusion: Paired BL and post-treatment biopsy analyses demonstrated a strong correlation between intrahepatic and serum HDV-RNA reductions. Reduced expression of infection-related genes accompanied the decline in HDV. The highest off-treatment virological response in the liver was observed in the arm that received BLV 10mg+PegIFNα combination.

Publication History

Article published online:
20 January 2025