Remibrutinib demonstrates favorable safety profile and sustained efficacy in chronic spontaneous urticaria over 52 weeks.

Abstract

BACKGROUND:

Remibrutinib (LOU064), an oral, highly selective Bruton tyrosine kinase inhibitor, offers fast disease control in patients with chronic spontaneous urticaria (CSU) who remain symptomatic despite treatment with second-generation H1 antihistamines. It is currently in phase 3 development for CSU.

OBJECTIVE:

We sought to evaluate long-term safety and efficacy of remibrutinib in patients with CSU inadequately controlled with H1 antihistamines.

METHODS:

In this phase 2b extension study, patients who completed the core study and had a weekly Urticaria Activity Score (UAS7) ≥16 at the beginning of the extension study received remibrutinib 100 mg twice daily for 52 weeks. The primary objective was to assess long-term safety and tolerability. Key efficacy end points included change from baseline in UAS7 and proportion of patients with complete response to treatment (UAS7 = 0) and well-controlled disease (UAS7 ≤6) at week 4 and over 52 weeks.

RESULTS:

Overall, 84.3% (194/230) of patients entered the treatment period and received ≥1 doses of remibrutinib. The overall safety profile of remibrutinib was comparable between the extension and core studies. Most treatment-emergent adverse events were mild to moderate and considered unrelated to remibrutinib by investigators. The 3 most common treatment-emergent adverse events by system organ class were infections (30.9%), skin and subcutaneous tissue (26.8%), and gastrointestinal disorders (16.5%). At week 4 and 52, mean ± SD change from baseline in UAS7 was -17.6 ± 13.40 and -21.8 ± 10.70; UAS7 = 0 (as observed) was achieved in 28.2% and 55.8% and UAS7 ≤6 (as observed) was achieved in 52.7% and 68.0% of patients, respectively.

CONCLUSIONS:

Remibrutinib demonstrated a consistent favorable safety profile with fast and sustained efficacy for up to 52 weeks in patients with CSU.

• Authors: Vipul Jain, Ana Giménez-Arnau, Koremasa Hayama, Adam Reich, Warner Carr, Jeffrey Tillinghast, Swapnil Dahale, Karine Lheritier, Pauline Walsh, Artem Zharkov, Sophie Hugot, Sibylle Haemmerle
• Journal: The Journal of allergy and clinical immunology (J Allergy Clin Immunol) Vol. 153 Issue 2 Pg. 479-486.e4 (Feb 2024) ISSN: 1097-6825 [Electronic] United States
• PMID: 37866460 (Publication Type: Journal Article)
• Copyright: Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.

Chemical References

• Anti-Allergic Agents
• Omalizumab
• remibrutinib
• Histamine H1 Antagonists
• Pyrimidines

Topics

• Humans
• Anti-Allergic Agents (therapeutic use)
• Omalizumab (therapeutic use)
• Treatment Outcome
• Chronic Disease
• Chronic Urticaria (drug therapy)
• Urticaria (drug therapy, chemically induced)
• Histamine H1 Antagonists (therapeutic use)
• Pyrimidines