Fast symptom improvement and favorable safety profile with remibrutinib in chronic spontaneous urticaria: remix-1/-2 studies

IntroductionRemibrutinib is an oral, highly selective Bruton's tyrosine kinase inhibitor. Here we present primary analyses of phase 3 studies evaluating its efficacy and safety in chronic spontaneous urticaria (CSU).MethodsREMIX-1 and REMIX-2 are global, double-blind, placebo-controlled trials. Patients ≥18y with CSU inadequately controlled by second-generation H1-antihistamines were randomized 2:1 to remibrutinib 25 mg twice-daily or placebo (24 weeks), followed by open-label treatment with remibrutinib (28 weeks). Primary endpoint scenarios were change from baseline (CFB) in weekly 1) Urticaria Activity Score (UAS7) and 2) Itch Severity Score (ISS7) and Hives Severity Score (HSS7) at week 12. Treatment-emergent adverse events (AEs) and laboratory parameters were assessed.ResultsOverall, 470 and 455 patients were randomized in REMIX-1 (remibrutinib, n=313; placebo, n=157) and REMIX-2 (remibrutinib, n=300; placebo, n=155), respectively. Baseline UAS7 (mean±SD) for remibrutinib and placebo was 30.7±7.9 and 29.7±7.6 (REMIX-1) and 30.2±8.0 and 29.5±7.5 (REMIX-2). Remibrutinib demonstrated fast (as early as week 2) and superior improvements vs placebo in CFB-UAS7 (least squares mean±SE; REMIX-1: −20.1±0.7 vs −13.8±1.0; REMIX-2: −19.6±0.7 vs −11.7±0.9), CFB-ISS7, and CFB-HSS7 at week 12 (Table). AEs with remibrutinib were comparable to placebo (59.9% vs 56.2% [REMIX-1]; 68.4% vs 73.2% of patients [REMIX-2]), with balanced liver function tests across studies.ConclusionIn the pivotal REMIX studies, both primary endpoint scenarios (CFB-UAS7, CFB-ISS7/CFB-HSS7) were met. Remibrutinib demonstrated a fast onset of action, superiority to placebo in improving CSU symptoms, and a favorable safety profile, suggesting remibrutinib may be an effective oral treatment for patients with CSU inadequately controlled by antihistamines.