Background/Purpose: Acute gouty arthritis(GA) is a common and debilitating condition, especially for patients unsuitable for standard therapy. Firsekibart, previously called Genakumab, is a first-in-class fully IgG4/λ anti-human-IL-1β monoclonal antibody, making it a significant option for gout treatment.

Methods: This phase III clinical trial was a multicenter, randomized, double-blind, double-dummy, active-controlled study conducted from Jan. 2023 to Jun. 2024 across 51 centers in China (NCT05983445). Patients aged 18–75 years with GA, contraindicated of, intolerance of, or unresponsiveness to NSAIDs and/or colchicine, with ≥2 episodes during the last 12 months were screened for eligibility.Patients were randomized 1:1 to receive a single subcutaneous dose of Firsekibart (200 mg) or an intramuscular dose of CB 7 mg.The co-primary endpoints were change in pain intensity from baseline to 72 hours in the most affected joint measured on VAS (0–100 mm) and the time to first new episode over 12 weeks. Secondary endpoints included: change in VAS scores at other time points(6h, 24h, 48h, 7 days post-dose), time to reduce 50% pain,proportion of patients experiencing ≥ 1 new flare, the mean flare rate per patient over 12 and 24 weeks, proportion of patients requiring rescue therapy,the dosage of rescue medicine and safety assessments.

Results: The full analysis included 311 patients, with 156 receiving Firsekibart and 155 receiving CB. The median age was 42, 89.4% patients had ≥ 3 flares in the last 12 months. Firsekibart significantly delayed median time to first new flare (Not estimable vs. 45 days) and reduced risk of new flare by 90% (HR0.10; 95% CI: 0.06, 0.17; p< 0.0001) over 12 weeks, by 87% (HR 0.13; 95% CI: 0.08, 0.21; p< 0.0001) over 24 weeks. Although the reduction of pain intensity and the median time to reduce ≥50% pain were similar，Firsekibart showed better pain relief in GA patients from 48 hours to 7 days. Significantly fewer patients treated with Firsekibart experienced ≥ 1 new flare over 12 weeks and 24 weeks ( 10.9% vs. 65.2%, 14.7% vs. 66.5%, p < 0.0001), and the mean number of new flares per patient was lower in Firsekibart group over 12 and 24 weeks (0.2 (0.52) vs. 1.2 (1.27), 0.2 (0.79) vs. 1.6 (1.79)) (mean(SD)). A smaller proportion of patients in the Firsekibart group required rescue therapy (10.9% vs 48.4%). Less mean dosage of rescue medicine was uesd in Firsekibart group (corticosteroid was 69.33 mg vs 202.03 mg).The overall incidence of treatment-emergent adverse event (TEAE) was comparable, occurring in 111 patients (71.2%; grade ≥3: 12.2%) in the Firsekibart group and 109 patients (69.9%; grade ≥3: 10.9%) in the CB group. The most common TEAE in Firsekibart group was hypertriglyceridaemia(27.6%; grade ≥3: 10.3%), and it may own to the high proportion of patients with dyslipidemia at baseline. Neither extra safety risk for patients with abnormal liver or kidney function nor treatment-related serious adverse events(TRSAE) were reported in Firsekibart group. All 3 TRSAE were reported in CB group.

Conclusion: Firsekibart is effective and well-tolerated for acute gout flares in patients with limited treatment options, demonstrating rapid pain relief and significant superiority in preventing flare compared with CB.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/efficacy-and-safety-of-firsekibart-in-acute-gouty-arthritis-patients-with-limited-treatment-options-a-multicenter-randomized-double-blind-double-dummy-active-controlled-phase-iii-trial/