BulevirtideHEPCLUDEX

7.1 The PBAC deferred making a recommendation for the listing of bulevirtide for treatment of chronic hepatitis delta virus (CHD) infection. While the PBAC was of a mind to recommend bulevirtide, the PBAC noted that an integrated codependent submission for the MBS listing of Hepatitis D ribonucleic acid polymerase chain reaction testing for CHD would be considered at the April 2025 MSAC meeting.PSD · Mar 2025

OFFICIAL Public Summary Document – March 2025 PBAC Meeting with July 2025 Addendum PBAC also considered the proposed utilisation of bulevirtide was uncertain but the estimates presented in the submission appeared to be reasonable.PSD · Mar 2025

6.43 The resubmission presented an updated modelled economic evaluation based on virological response rates (defined as undetectable HDV RNA or decrease in HDV RNA by ≥2 log IU/mL from baseline) reported up to Week 144 in the MYR301 trial that 10 compared bulevirtide treatment to BSC (delayed treatment) in patients with HDV RNA positive CHD. The key components of the economic evaluation are summarised in 24 OFFICIALPSD · Mar 2025

OFFICIAL Public Summary Document – March 2025 PBAC Meeting with July 2025 Addendum Table 12. The ESCs considered that PBAC’s advice that the most appropriate way to manage the substantial uncertainties in the economic model would be to adopt a conservative approach to the model inputs (paragraph 7.14 bulevirtide PSD, March 2024 PBAC Meeting) was not addressed in the resubmission or the PSCR.PSD · Mar 2025

6.34 The resubmission described bulevirtide as superior, in terms of effectiveness compared to current symptomatic management of CHD or BSC. The comparative evidence from the MYR301 trial demonstrated treatment effects associated with bulevirtide over BSC regarding virological response (undetectable HDV RNA or HDV RNA ≥ 2 log IU/mL reduction from baseline), biochemical endpoint (ALT 10 normalisation) and liver stiffness at Week 48.PSD · Mar 2025

6.35 The resubmission described bulevirtide as having a manageable safety profile compared to symptomatic management of CHD or BSC. The ESCs agreed with the evaluation that this claim was partially supported by the evidence presented. Even though most AEs observed in the MYR301 trial were mild to moderate in severity and no AEs led to withdrawal from the study treatment, the small sample size of the trial (N = 49) is of concern.PSD · Mar 2025

6.2 The PBAC noted and welcomed the input from consumer group/organisations (2) via the Consumer Comments facility on the PBS website. The PBAC noted the comments from Hepatitis Australia and Liver Foundation supporting the listing of bulevirtide noting there is a high unmet demand for effective hepatitis D treatment.PSD · Mar 2025

6.6 The risk of bias was considered high for the studies which informed assessments of the accuracy and performance of the test, prognostic value of HDV RNA and change in patient management. The overall risk of bias in the trial (MYR301) was considered low. The limitation of the MYR301 trial design was the open-label design of the study, in which patients and investigators were not blinded to the treatment group assignment.PSD · Mar 2025