Global 
Deutschland Liver and Bile
Gut. 2025;74(3):440-450
Long-term hepatitis B surface antigen response after finite treatment of ARC-520 or JNJ-3989
Background and aims: RNA interference has been extensively explored in patients with chronic hepatitis B (CHB) infection. The aim of this study was to characterise the long-term efficacy of small interfering RNA (siRNA) on hepatitis B surface antigen (HBsAg) suppression.
Methods: The authors prospectively followed up participants with CHB who received siRNA, either ARC-520 or JNJ-73763989 (JNJ-3989), in combination with nucleoside analogue (NUC) in their centre. Participants enrolled included 15 receiving 4 monthly injections of ARC-520, 38 receiving 3 injections of JNJ-3989 at 1, 2 or 4 weekly intervals and 5 receiving placebo in previous clinical trials. Serial blood sampling was performed according to the original protocols and on completion every 24 weeks until last follow-up (LFU) with mean duration of 52.5 months.
Results: Among the 53 NUC+siRNA-treated participants (mean age 46.8, baseline HBsAg 3.08 log, 83% previously on NUC, 34% hepatitis B e antigen+), the proportion of patients achieving HBsAg seroclearance or < 100 IU/ml at LFU was 1.9% and 32.1%, respectively, compared with 0% and 0% for placebo. Among siRNA-recipients, 48.5% and 5.0% of those with HBsAg < 100 IU/ml and > 100 IU/ml at nadir or ≤ 24 weeks from last dose could maintain or achieve HBsAg < 100 IU/ml at LFU, respectively. Compared with placebo recipients, siRNA-recipients demonstrated faster overall annual decline of HBsAg (0.08 vs. 0.21 log IU/ml/year) contributed predominantly by changes in the first year. Age was negatively correlated with HBsAg reduction at LFU (r = -0.427, p = 0.001).
Conclusion: Short-duration small interfering RNA treatment suppressed HBsAg expression with a prolonged effect for up to 6 years in some participants.