Remibrutinib: A Novel BTKi in Development for MS With a Favorable Safety Profile in Various Autoimmune Disorders
Mitzi Williams1, Laura Airas2, Tanuja Chitnis3, Sarbjit Saini4, Michihiro Hide5, Gordon Sussman6, Jin Nakahara7, Robert Bermel8, Thomas Dörner9, Brett Loop10, Marina Ziehn11, Roman Willi11, Bernd C. Kieseier12, Ivan Nikolaev11, Sibylle Haemmerle11, Artem Zharkov11, Richard Siegel13, Bruno Cenni13, Heinz Wiendl14, Marcus Maurer15, Ana Giménez-Arnau16, Xavier Montalban17
1Joi Life Wellness Group, Atlanta, GA, USA, 2Turku University Hospital and University, Finland, 3Brigham and Women's Hospital, Department of Neurology, Boston, MA, USA, 4Johns Hopkins Asthma and Allergy Center, Baltimore, MD, USA, 5Hiroshima City Hiroshima Citizens Hospital, Hiroshima, Japan, 6University of Toronto, Toronto, Ontario, Canada, 7Department of Neurology, Keio University School of Medicine, Tokyo, Japan, 8Mellen Center for MS, Cleveland Clinic, Cleveland, OH, USA, 9Department of Rheumatology and Clinical Immunology, Charite Universitätsmedizin Berlin; DRFZ, Berlin, Germany, 10Novartis Pharmaceutical Corporation, Cambridge, MA, USA, 11Novartis Pharma AG, Basel, Switzerland, 12Novartis Pharma AG, Basel, Switzerland; Department of Neurology, Heinrich-Heine University, Duesseldorf, Germany, 13Novartis Institutes for Biomedical Research, Basel, Switzerland, 14Department of Neurology with Institute of Translational Neurology, University of Münster, Münster, Germany, 15Urticaria Center of Reference and Excellence (UCARE), Institute of Allergology, Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany; Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Allergology and Immunology, Berlin, Germany, 16Department of Dermatology, Hospital del Mar - IMIM, Universitat Pompeu Fabra, Barcelona, Spain, 17Department of Neurology-Neuroimmunology, Centre d'Esclerosi Múltiple de Catalunya (Cemcat), Hospital Universitari Vall d'Hebron, Barcelona, Spain
Objective:
To report the safety of remibrutinib from Phase 2 clinical trials in various autoimmune disorders.
Background:
Remibrutinib, a potent, highly selective, covalent, oral Bruton's tyrosine kinase inhibitor, is currently being investigated in Phase 3 trials for the treatment of multiple sclerosis (MS; NCT05147220/NCT05156281). Remibrutinib showed a favorable selectivity and potency profile in vitro, with the potential to minimize off-target toxicity and associated adverse events (AEs).
Design/Methods:
This safety overview reports data from a final analysis of Phase 2 trials in chronic spontaneous urticaria (CSU), Sjögren syndrome (SjS), and asthma, and interim analysis of the open-label extension (OLE) in CSU. Safety assessments comprised AEs, including serious and AEs of special interest (AESI), vital signs, ECGs, and laboratory parameters.
Results:
Overall, 363 patients (267, CSU; 49, SjS; 47, asthma) who received various doses (10–100 mg q.d./b.i.d.) of remibrutinib for 12–52 weeks were included. For CSU, 267 patients received different doses in the core study; in the OLE, 183 received 100 mg b.i.d. Safety of remibrutinib in the core study was comparable across dose levels. Similarly, in the OLE, safety of remibrutinib 100 mg b.i.d. was comparable to any dose in the core. For CSU, SjS, and asthma, the most frequently reported grouped AEs (≥10%) were Infections and infestations, Skin and subcutaneous, Gastrointestinal, and Nervous system disorders. Overall, AEs were comparable to placebo in core studies, with no increases in infection rates and except for skin disorders where CSU flares caused an imbalance. AESI including bleeding, infection and cytopenia remained stable with long-term treatment. No safety concerns were noted in the analysis of laboratory parameters, ECGs and vital signs.
Conclusions:
Remibrutinib demonstrated a favorable safety profile and was well tolerated at all doses studied in Phase 2 trials and the OLE (up to 100 mg b.i.d.), supporting its development in Phase 3 clinical trials in MS.