Remibrutinib in chronic spontaneous urticaria: 52-week results from two phase 3 studies
Ana M. Giménez‐Arnau, R. Szalewski, Michihiro Hide, Vipul Jain, A. Khemis, Mark Lebwohl, Martin Metz, Giselle Mosnaim, Michael Palumbo, Ekin Şavk, Gordon Sussman, Irena Walecka-Herniczek, Bin Yang, Claire Field, Sibylle Haemmerle, K. Lheritier, P.G.P Machado, E.D. Martzloff, Noriko Seko, Pengpeng Wang, Artem Zharkov, Sarbjit S. Saini
Abstract
Background Remibrutinib, an oral, highly selective Bruton tyrosine kinase inhibitor, demonstrated significant improvements in disease activity over placebo in the 24-week phase 3 REMIX studies in patients with chronic spontaneous urticaria (CSU) remaining symptomatic despite second-generation H 1 -antihistamines. Objective We sought to evaluate the long-term efficacy and safety of remibrutinib in patients with CSU. Methods REMIX-1 (NCT05030311) and REMIX-2 (NCT05032157) were two randomized placebo-controlled studies evaluating the efficacy, safety, and tolerability of remibrutinib in patients with CSU. Patients were randomized 2:1 to receive oral remibrutinib 25 mg twice daily or placebo during a 24-week double-blind placebo-controlled period, followed by a 28-week open-label treatment period (up to 52 weeks). The primary end point was change from baseline in weekly Urticaria Activity Score at week 12. Results A total of 470 patients in REMIX-1 and 455 in REMIX-2 were randomly assigned to receive remibrutinib (n = 313 and 300, respectively) or placebo (n = 157 and 155, respectively). At week 52, patients randomized to remibrutinib showed sustained improvements in change from baseline in weekly Urticaria Activity Score (mean [95% confidence interval], REMIX-1: −23.22 [−24.78, −21.66]; REMIX-2: −22.98 [−24.51, −21.44]), with similar responses observed in patients who transitioned from placebo to remibrutinib at week 24 (observed as early as 1 week after transitioning). Exposure-adjusted incidence rates of adverse events, serious adverse events, and adverse events leading to discontinuation with 52-week remibrutinib treatment remained equivalent to those in the 24-week analysis. Conclusion Remibrutinib showed sustained efficacy and a consistent, favorable long-term safety profile in patients with CSU remaining symptomatic despite second-generation H 1 -antihistamines.