Remibrutinib shows promising efficacy and safety in chronic spontaneous urticaria

Published: September 9, 2022

Chronic spontaneous urticaria (CSU), a debilitating skin condition, is characterized by the occurrence of itchy wheals (hives) and/or angioedema, for longer than 6 weeks and usually many years. CSU has a detrimental impact on the quality of life of patients. Many patients with CSU respond inadequately to currently approved therapies, second-generation H1 antihistamines and omalizumab (an anti-immunoglobulin E (IgE) monoclonal antibody). There is a considerable unmet need for effective new therapies for CSU with a novel mechanism of action. Remibrutinib (LOU064), a novel, highly selective, potent, covalent, oral Bruton’s tyrosine kinase (BTK) inhibitor, may be a potential treatment option for CSU.

In a recent article in The Journal of Allergy and Clinical Immunology (JACI), Maurer et al. report key results of a Phase 2b study, which investigated the efficacy and safety of remibrutinib in patients with moderate to severe CSU, with or without prior anti-IgE treatment. Patients with at least moderately active CSU, inadequately controlled by second-generation H1-antihistamines for ≥6 months with a weekly urticaria activity score (UAS7) ≥16 and a weekly Hives Severity Score (HSS7) of ≥8 were enrolled in the study. Patients were equally randomized to receive remibrutinib 10 mg, 35 mg or 100 mg once-daily, or 10 mg, 25 mg or 100 mg twice-daily, or placebo. The primary endpoint of the study was change in UAS7 from baseline at Week 4. The key secondary endpoints included change from baseline in UAS7 at Week 12 and over time, proportion of patients with a complete absence of hives and itch (UAS7=0) and well-controlled disease (UAS7≤6) over time, and safety and tolerability of remibrutinib.

The primary endpoint of the study was met. Remibrutinib (all doses) significantly improved the signs and symptoms of CSU; a dose-response change from baseline in UAS7 was observed versus placebo at Week 4. All remibrutinib doses significantly improved UAS7 from baseline versus placebo at Week 4, and results were sustained at Week 12. A rapid improvement in UAS7 was observed for all remibrutinib doses as early as Week 1, which was maintained for up to Week 12. More patients in any of the remibrutinib dose achieved complete absence of hives and itch (UAS7=0) and a well controlled disease (UAS7≤6) over the 12 weeks compared to placebo. Overall, the incidence of adverse events among patients receiving remibrutinib was comparable to that of patients on placebo. Most of the adverse events were mild/moderate in nature, with no dose-dependent pattern in terms of types and severity of events.

Results from the Phase 2b study showed that remibrutinib is an effective treatment for CSU over the entire dose range tested, with a rapid onset of action and a favorable safety profile. Remibrutinib has the potential to become a preferred oral treatment option for patients with CSU.

The Journal of Allergy and Clinical Immunology (JACI) is an official scientific journal of the AAAAI and is the most-cited journal in the field of allergy and clinical immunology.

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