The combination of xalnesiran with pegylated interferon alfa-2a resulted in 23% of chronic hepatitis B patients with baseline hepatitis B surface antigen (HBsAg) levels below 1000 IU/mL achieving HBsAg loss at 24 weeks after completing a 48-week treatment, according to a recent study published in The New England Journal of Medicine.

This phase 2, multicenter, randomized, controlled, open-label platform trial assessed the efficacy and safety of xalnesiran, a small interfering RNA molecule, alone or in combination with immunomodulators, in patients with chronic hepatitis B virus (HBV) infection. The study included 159 participants with virologic suppression on nucleoside/nucleotide analog (NA) therapy for at least 12 months. Participants were randomly assigned to one of five groups: xalnesiran 100 mg (group 1), xalnesiran 200 mg (group 2), xalnesiran 200 mg plus ruzotolimod 150 mg (group 3), xalnesiran 200 mg plus pegylated interferon alfa-2a 180 μg (group 4), or NA therapy alone (group 5). The primary endpoint was HBsAg loss, defined as levels below 0.05 IU/mL, evaluated 24 weeks after treatment.

At 24 weeks post-treatment, HBsAg loss was achieved by 23% of participants in group 4 compared to 7% in group 1, 3% in group 2, 12% in group 3, and none in group 5. Seroconversion rates were highest in group 4 at 20%. HBsAg loss occurred exclusively in participants with baseline HBsAg levels below 1000 IU/mL, with group 4 demonstrating the most significant response (47%). However, durability of HBsAg loss in group 4 decreased from 78% at 24 weeks to 56% at 48 weeks post-treatment.

Safety analysis revealed that grade 3 or 4 adverse events were most frequent in group 4 (50%), primarily elevated alanine aminotransferase (ALT) levels, which occurred in 13% of participants in this group. Adverse events related to liver enzyme elevations were asymptomatic and resolved without evidence of liver dysfunction.

Participants were predominantly male (83%) and of Asian descent (94%), which may limit generalizability. The trial highlighted the potential for finite-duration therapy in achieving HBsAg loss but emphasized the need for longer follow-up to assess durability.

Full disclosures are available in the published study.