BTK Inhibitor Remibrutinib Demonstrates Positive Safety in Various Autoimmune Disorders

Laura Airas, MD, PhD

In a recent analysis, investigational agent remibrutinib (Novartis) showed a positive safety profile and was well tolerated at all doses for up to 100 mg twice a day among patients with various autoimmune disorders.¹ These findings further support the investigation of remibrutinib, a novel, potent, highly selective, covalent, oral Bruton’s tyrosine kinase inhibitor (BTKi), for the treatment of multiple sclerosis (MS) in current phase 3 clinical trials.

Data was collected from 267 patients with chronic spontaneous urticaria (CSU), 49 patients with Sjögren syndrome (SjS), and 47 patients with asthma, as well as an interim analysis of a 52-week open label extension (OLE) study in CSU. Among the selected from the trials, a total of 363 patients received different doses of remibrutinib, ranging between 10mg and 100 mg every day or twice a day, for 12 to 52 weeks.

Presented at the 9th Congress of the European Academy of Neurology, held July 1-4, in Budapest, Hungary, by lead author Laura Airas, MD, PhD, professor of neuroimmunology at Turku University Hospital and University of Turku in Finland and colleagues, the analysis provided an broad overview remibrutinib’s safety using clinical trials on various autoimmune disorders. The safety of remibrutinib 100 mg twice daily in the OLE study was compared with the doses patients with CSU received in the original study.

Safety was assessed according to reports of adverse events (AEs), including serious and AEs of special interest (AESI), as well as vital signs, electrocardiogram (ECGs), and laboratory parameters. AEs that occurred in more than 10% of treated patients on remibrutinib included infections and infestations, skin, subcutaneous, gastrointestinal, and nervous system disorders.

Notably, the AE profile of remibrutinib was similar with the placebo group in the original research studies of the trials excluding skin disorders, where imbalance was caused from post-treatment for CSU flares. All told, infection rates had no increase among patients and other AESI such as bleeding, which were all minor, and cytopenia were unchanged during long-term treatment. Authors noted that there were no safety concerns that were reported in the laboratory analyses, ECGs, or vital signs.

Currently, the highly selective BTK inhibitor is being investigated in phase 3 clinical trials for relapsing multiple sclerosis (NCT05147220/NCT05156281). These trials will compare remibrutinib with teriflunomide (Aubagio; Sanofi) and will primarily focus on the annual relapse-rate outcomes as well as confirmed disability progression, neurofilament light chain levels, new Gd-enhancing lesions, and physical function.²

Although remibrutinib does not have final analyses yet in clinical trials for MS, the treatment was well tolerated in healthy subjects and patients with asymptomatic atopic diathesis (NCT03918980). All told the therapy in the trial, “demonstrated a very fast onset of action and full BTK occupancy for at least 24 hours post-single doses of 30 mg and higher, while repeated dosing did not cause accumulation.”²

Remibrutinib was also assessed in a phase 2 trial (NCT03926611) and open-label extension of 311 patients with CSU controlled inadequately by H1 antihistamines. Findings showed that all tested doses of remibrutinib displayed significant improvements in urticaria activity score change from baseline at week 4 and week 12 compared with placebo.³

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REFERENCES
1. Airas L, Williams M, Chitnis T, et al. Remibrutinib: A Novel BTKi in Development for MS With a Favorable Safety Profile in Various Autoimmune Disorders. EPO-146.
2. Geladaris A, Torke S, Weber MS. Bruton's Tyrosine Kinase Inhibitors in Multiple Sclerosis: Pioneering the Path Towards Treatment of Progression?. CNS Drugs. 2022;36(10):1019-1030. doi:10.1007/s40263-022-00951-z
3. Mendes-Bastos P, Brasileiro A, Kolkhir P, et al. Bruton's tyrosine kinase inhibition-An emerging therapeutic strategy in immune-mediated dermatological conditions. Allergy. 2022;77(8):2355-2366. doi:10.1111/all.15261