Treatment with bulevirtide monotherapy for up to 144 weeks is safe, well tolerated, and effective in patients with chronic hepatitis D (CHD), a study has shown.
Specifically, improvements have been noted in combined, virologic, and biochemical response rates, with sustained increases in undetectable hepatitis D virus (HDV) RNA from 96 to 144 weeks of treatment.
“Response rates decreased after treatment discontinuation, [but] some patients had sustained undetectable HDV RNA throughout 2 years of follow-up,” the researchers said.
In this study, 150 patients with CHD were randomized to receive immediate treatment with bulevirtide 2 mg/day (n=49) or 10 mg/day (n=50) for 144 weeks or to a 48-week delay before initiating treatment (DT; n=51), followed by bulevirtide 10 mg/day for 96 weeks (DT/10 mg; n=50), and 96 weeks of post-treatment follow-up (FU96) in the MYR301 study.
The efficacy endpoints were as follows: virologic response (VR; undetectable HDV RNA or ≥2 log10 IU/ml decline from baseline), combined response (CR; VR and alanine aminotransferase [ALT] normalization), ALT normalization, and undetectable HDV RNA.
Response rates at the end of treatment (EOT) in the 2-, 10-, and DT/10-mg groups were 73 percent, 76 percent, and 92 percent for VR; 59 percent, 60 percent, and 58 percent for ALT normalization; 57 percent, 54 percent, and 56 percent for CR; and 29 percent, 50 percent, and 52 percent for HDV RNA, respectively. [J Hepatol 2026;85:493-503]
Undetectable HDV RNA
VR rates decreased to 33 percent, 30 percent, and 32 percent in the 2-, 10-, and DT/10-mg groups at FU96, while CR rates were 24 percent across groups. Undetectability rates of HDV RNA at FU96 were 20 percent, 22 percent, and 20 percent, respectively.
“Sustained undetectability through follow-up was observed in 23 of 64 (36 percent) patients with undetectable HDV RNA at EOT, with weeks continuously undetectable at EOT being the most important predictor of sustained undetectability,” the researchers said.
The duration of continuous on-treatment undetectability at EOT showed a robust relationship with sustained undetectability post-treatment. Patients with at least 96 weeks of continuous undetectable HDV RNA at EOT had the lowest odds of relapse.
These findings suggest the possibility of treatment cessation in patients who achieve and maintain undetectable HDV RNA on bulevirtide monotherapy for over 2 years, independent of cirrhosis status. [J Hepatol 2023;78:876-880]
“However, further studies are needed to validate these findings, as most patients require continued bulevirtide therapy to maintain virologic and biochemical improvements and prevent liver disease progression,” the researchers said.
With respect to safety, hepatic serious adverse events occurred in 20 of 142 (14 percent) patients post-treatment and resolved in 17 of 20 (85 percent).
“Additionally, the risk of post-treatment hepatitis flares after treatment discontinuation should be carefully considered, especially in patients with cirrhosis who may be at risk of more severe flares,” the researchers said.
Bulevirtide is approved in the US, Australia, Canada, the European Economic Area, other European countries, and the Russian Federation. The European Association for the Study of the Liver also recommends this medication for CHD treatment. [J Hepatol 2023;79:433-460; J Hepatol 2025;83:502-583; https://www.accessdata.fda.gov/drugsatfda_docs/label/2026/761468Orig1s000lbl.pdf]