Population pharmacokinetics and exposure–response modelling of firsekibart (GenSci048) in patients with acute gout flare: Implications for fixed‐dose optimization

Background and Objectives Firsekibart (formerly GenSci048 or genakumab) is a humanized anti‐IL‐1β monoclonal antibody developed for acute gouty flares in patients unsuitable for standard therapies. This study characterized its population pharmacokinetics (PopPK), assessing covariate effects, and established exposure–response (E‐R) relationships to guide dosing. Methods Data from four clinical trials involving 296 subjects (2287 concentrations) were pooled to develop a PopPK model using NONMEM with stepwise covariate screening. A one‐compartment model with sequential zero‐ and first‐order absorption was utilized. E‐R analyses were conducted to assess efficacy (dVAS 72h , defined as achieving ≥50% reduction in Visual Analog Scale [VAS] scores from baseline measured at 72 h) and safety (dyslipidaemia/hepatic dysfunction/infectious and invasive diseases) using logistic regression. Results Body weight significantly affected clearance and distribution volume. Hepatic or renal impairment caused exposure differences of less than 27%. No exposure‐dependent safety trends were identified across the evaluated exposure range. Although exposure–response trends were observed across the broader dose range, the gradient within the exposure range achieved by 195–200 mg was shallow, consistent with a plateau. Simulations indicated that at the 200‐mg dose, more than 95% of patients attained exposures associated with at least 85% probability of achieving dVAS 72h . Firsekibart also markedly reduced flare recurrence over 12 weeks compared with the control group. Conclusion Firsekibart demonstrated predictable pharmacokinetics, a favourable safety profile, and robust efficacy coverage at the 200‐mg fixed dose. These findings support fixed‐dosing for patients with acute gout flares who are intolerant of, unsuitable for, or inadequately responsive to standard‐of‐care therapies.