Safety of Remibrutinib Across Immune-mediated Diseases Supports Development in Multiple Sclerosis
Bernd Kieseier1, Xavier Montalban2, Mitzi Williams3, Laura Airas4, Sarbjit Saini5, Michihiro Hide6, Gordon Sussman7, Jin Nakahara8, Robert Bermel9, Thomas Doerner10, Brett Loop11, Virginia DeLasHeras1, Roman Willi1, Sibylle Haemmerle1, Artem Zharkov1, Nathalie Barbier1, Amin Azmon1, Richard Siegel12, Bruno Cenni12, Heinz Wiendl13, Marcus Maurer14, Ana Gimenez-Arnau15, Tanuja Chitnis16
1Novartis Pharma AG, 2Department of Neurology-Neuroimmunology, Centre d'Esclerosi Múltiple de Catalunya (Cemcat), Hospital Universitari Vall d'Hebron, 3Joi Life Wellness Group, 4Turku University Hospital and University of Turku, 5Johns Hopkins Asthma and Allergy Center, 6Hiroshima Citizens Hospital, 7University of Toronto, 8Department of Neurology, Keio University School of Medicine, 9Mellen Center for MS, Cleveland Clinic, 10Department of Rheumatology and Clinical Immunology, Charite – Universitätsmedizin Berlin, 11Novartis Pharmaceutical Corporation, 12Novartis Institutes for Biomedical Research, 13Department of Neurology with Institute of Translational Neurology, University of Münster, 14Urticaria Center of Reference and Excellence, Institute of Allergology, Charité – Universitätsmedizin Berlin, 15Department of Dermatology, Hospital del Mar – IMIM, Universitat Pompeu Fabra, 16Department of Neurology, Brigham and Women's Hospital
Objective:
To report the integrated safety profile of remibrutinib using pooled data from completed phase 2 clinical trials in chronic spontaneous urticaria (CSU), Sjögren syndrome (SjS), and asthma, including long-term treatment up to 52 weeks.
Background:
Remibrutinib, a potent, highly selective, covalent, oral Bruton's tyrosine kinase inhibitor, is currently being investigated in 2 phase 3 trials for the treatment of relapsing multiple sclerosis (NCT05147220/NCT05156281). The high selectivity of remibrutinib has the potential to result in a favorable safety profile by minimizing off-target effects.
Design/Methods:
Pooled data from completed phase 2 studies of CSU (including the 52-week open-label extension), SjS, and asthma were analyzed. Safety assessments included adverse events (AEs), serious AEs (SAEs), and AEs of special interest (AESIs). Analyses were conducted for patients receiving any remibrutinib dose (n=391), and specifically for those receiving a 100-mg dose (n=327), using exposure-adjusted incidence rates (EAIRs) per 100 patient-years.
Results:
Patients receiving any remibrutinib dose had an EAIR of 260.8 for AEs, and the 100-mg subgroup had an EAIR of 224.8. The EAIR for AEs leading to treatment discontinuation was 8.3 for both groups, and the EAIR for SAEs was 4.2 for the any-dose group and 2.9 for the 100-mg subgroup. Infections and infestations were the most frequently reported grouped AESIs (EAIR, any dose: 68.0; 100 mg: 58.5) and were mild to moderate in severity, with mostly upper respiratory tract infections and nasopharyngitis. Other reported grouped AEs with EAIRs ≥20 were: skin/subcutaneous tissue disorders, gastrointestinal disorders, nervous system disorders, and musculoskeletal disorders. AESIs, other than infections, included bleeding (mostly minor cutaneous) and cytopenia (rare), which were mild to moderate in severity. Overall, EAIRs were generally similar for remibrutinib and placebo.
Conclusions:
This integrated safety analysis confirmed the consistently favorable safety profile of remibrutinib across indications and doses, including 100 mg twice daily, with ≤52 weeks of long-term exposure.