Arbutus Biopharma announced on April 15, 2026 that the US FDA granted Fast Track designation for imdusiran (AB-729) for the treatment of chronic hepatitis B (cHBV). The status allows earlier and more frequent agency interactions and, where criteria are met, eligibility for Accelerated Approval, Priority Review, or Rolling Review of a future marketing application.
Across its Phase IIa IM-PROVE I (NCT04980482) and IM-PROVE II (NCT06245291) trials, Arbutus reported that 10 patients with cHBV have achieved functional cure to date, defined as sustained HBsAg seroclearance and HBV DNA below the lower limit of quantification at 24 weeks off all treatment. Eight of those functional cures occurred within the Phase IIa trials themselves, with six of the eight patients sustaining that status for more than two years. Two additional patients reached functional cure during long-term follow-up after completing their trial participation. Separately, 41 patients across the Phase IIa program remained off nucleos(t)ide analogue (NA) therapy for at least 48 weeks following imdusiran-based combination treatment. In the IM-PROVE II cohort receiving imdusiran plus NA followed by the immunotherapeutic VTP-300 and low-dose nivolumab, 23% of participants achieved HBsAg loss by week 48, with HBsAg declines in that cohort statistically greater than in other arms (p=0.017). Seven of the eight functional cure patients had baseline HBsAg below 1,000 IU/mL. Imdusiran was described by the company as generally safe and well-tolerated across the program.
The IM-PROVE I trial enrolled HBeAg-negative, NA-suppressed patients with cHBV and evaluated imdusiran in combination with NA and pegylated interferon alfa-2a. IM-PROVE II incorporated additional cohorts, including a 20-patient arm receiving imdusiran plus NA for 24 weeks followed by VTP-300 and up to two low doses of nivolumab. The functional cure and off-therapy data reported by Arbutus are drawn from across both trials and the subsequent long-term follow-up period; the figures therefore reflect a heterogeneous patient population treated under different combination regimens. Formal efficacy analyses from the completed trials have not been separately published in peer-reviewed form based on the information available, and the 10 functional cure total spans multiple treatment arms and time periods.
Imdusiran is an RNAi therapeutic that targets hepatocytes via covalently conjugated N-acetylgalactosamine delivery technology, designed to suppress HBsAg and other HBV viral proteins as a prerequisite for immune-mediated viral control. Established NA therapies such as entecavir, which produced HBV DNA below 300 copies/mL in 76.4% of treatment-naive patients at week 96 in the BE-LOW study (NCT00410072), suppress viral replication without achieving functional cure in the majority of patients, which frames the clinical rationale for combination approaches targeting antigen clearance. Cross-trial comparisons are limited by differences in study design, duration, and patient populations.
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