Phase 3 Study to Evaluate Remibrutinib in Generalized Myasthenia Gravis

The randomized, double-blind, placebo-controlled, multicenter phase 3 RELIEVE (NCT06744920) is investigating the efficacy and safety of (Rhapsido; Novartis), a novel, highly selective, and potent covalent oral Bruton tyrosine kinase (BTK) inhibitor, in people with generalized myasthenia gravis (gMG). The trial will assess the change in myasthenia gravis activities of daily living (MG-ADL) total score from baseline to month 6.¹

The study, presented at the 2025 American Association of Neuromuscular & Electrodiagnostic Medicine meeting, held October 29 to November 1, in San Francisco, California, will enroll patients aged 18 to 75 years who are diagnosed with gMG and are either acetylcholine receptor positive, muscle-specific tyrosine kinase positive, or double-seronegative. To be eligible, patients must also have an MG-ADL score of 6 (> 50% nonocular) and be on stable standard-of-care treatment.

Approximately 180 participants will be observed with this investigation; they will be randomized 1:1 to receive either remibrutinib or placebo during the 6-month double-blind core treatment period. The trial will be followed by an open-label extension with remibrutinib treatment for up to 60 months.

This study is not the first time remibrutinib has been tested for safety. Two years ago, published data showed that the BTK inhibitor had a positive safety profile and was well tolerated at all doses up to 100 mg twice a day among patients with various autoimmune disorders. These findings further supported the investigation of remibrutinib for the treatment of multiple sclerosis in phase 3 clinical trials.²

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

That analysis was originally presented at the 9th Congress of the European Academy of Neurology, held July 1-4, in Budapest, Hungary, and provided a broad overview of remibrutinib’s safety using clinical trials on various autoimmune disorders. In the open-label extension study, the safety of remibrutinib 100 mg twice daily was compared with the doses that patients with chronic spontaneous urticaria received in the original study.

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

Recently, Novartis received FDA approval for remibrutinib, the first and only oral BTK inhibitor for adults with chronic spontaneous urticaria who remain symptomatic despite antihistamine therapy. The twice-daily pill offers a targeted approach to controlling the itching and hives of CSU by blocking BTK activity, an immune pathway that drives histamine and inflammatory mediator release.³ Lab monitoring is not required.

The FDA approval of remibrutinib was based on results from the phase 3 REMIX-1 (NCT05030311) and REMIX-2 (NCT05032157) clinical trials in patients who remained symptomatic on second-generation H1 antihistamines. More patients treated with remibrutinib vs placebo achieved well-controlled disease (Urticaria Activity Score ([a 7-day measure] ≤ 6) as early as week 2. Also, at week 12, about 33% of patients achieved complete absence of itch and hives. The most common AEs (incidence ≥ 3%) were nasal congestion, sore throat, runny nose, bleeding, headache, nausea, and abdominal pain.

References

1. Willi R, Bril V, Howard J, et al. RELIEVE: a phase 3 study evaluating the efficacy and safety of remibrutinb in generalized myasthenia gravis. Presented at: American Association of Neuromuscular & Electrodiagnostic Medicine Annual Meeting; October 29-November 1, 2025; San Francisco, California.

2. 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. Presented at: Congress of the European Academy of Neurology; July 1-4, 2023; Budapest, Hungary. Poster EPO-146.

3. Novartis receives FDA approval for Rhapsido (remibrutinib), the only oral, targeted BTKi treatment for chronic spontaneous urticaria (CSU). News release. Novartis. September 30, 2025. Accessed November 6, 2025. https://www.novartis.com/news/media-releases/novartis-receives-fda-approval-rhapsido-remibrutinib-only-oral-targeted-btki-treatment-chronic-spontaneous-urticaria-csu