Efficacy and Safety of Firsekibart in Patients with Acute Gout Unsuitable for Standard Therapy: 48-Week Results from an Open-Label Extension of a Randomized Phase 3 Trial

INTRODUCTION: Patients with recurrent acute gout flares who are unable to use nonsteroidal anti-inflammatory drugs (NSAIDs) or colchicine have limited alternatives and remain at high risk of flare recurrence. Firsekibart is a fully human monoclonal antibody targeting interleukin-1βeta (IL-1β) The objective of this study is to evaluate the longer-term efficacy and safety of firsekibart through 48 weeks in patients with acute gout unsuitable for standard anti-inflammatory therapy. METHODS: This was a multicenter, randomized, double-blind, positive-controlled phase 3 study of firsekibart with compound betamethasone. Followed by a 24-week open-label extension (OLE), conducted at hospitals in China. The double-blind phase was conducted from Week 0 to Week 24, followed by an OLE through Week 48 and a 12-week safety follow-up period after the last dose. Adults with ≥ 2 acute gout flares in the past year and a contraindication, intolerance, or inadequate response to NSAIDs and/or colchicine were enrolled. Patients completing the double-blind phase entered the OLE, during which firsekibart was administered for acute gout flares as needed. Efficacy included proportion of patients experiencing ≥ 1 gout flare recurrence, number of flares per patient, and time to first recurrence through Week 48, as well as rescue medication use during the OLE. Exploratory outcomes included health-related quality of life and flare-related pain. Safety included adverse events (AEs), laboratory tests, and immunogenicity. RESULTS: Of 313 patients (double-blind phase), 300 entered the OLE. By week 48, gout flare recurrence occurred in 70 patients (44.9%) in the firsekibart group compared with 116 (74.8%) in the positive control group (difference - 29.97%; 95% CI - 40.228% to - 18.544%). Kaplan-Meier analysis showed that the median time to first recurrence was not reached with firsekibart versus 37 days with positive control, indicating a 70% [hazard ratio (HR) 0.30; 95% confidence interval (CI) 0.223, 0.408; stratified log rank P < 0.0001] lower recurrence risk. Firsekibart maintained efficacy through Week 48. Treatment-emergent adverse events were reported in 89.7% of patients in the firsekibart group and 89.1% in the positive control group, with no new safety signals identified during extended follow-up. CONCLUSION: In this open-label extension study, firsekibart demonstrated sustained efficacy in reducing gout flare recurrence through 48 weeks, with a consistent and favorable safety profile, and no new safety signals identified during extended follow-up. TRIAL REGISTRATION: NCT05983445.