New Phase 3 Study to Evaluate Remibrutinib in Generalized Myasthenia Gravis Treatment

A randomized, double-blind, placebo-controlled, multicenter phase 3 study, dubbed RELIEVE (NCT06744920), is investigating the efficacy and safety of remibrutinib (Novartis), a novel, highly selective and potent, covalent, oral BTK inhibitor, in people with general myasthenia gravis (gMG). The 6-month trial will assess the change in myasthenia gravis activities of daily living score (MG-ADL) total score from baseline to month 6.

The study, presented at the 2025 American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM) 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 (AChR+), muscle-specific tyrosine kinase positive (MuSK+), or double-seronegative (AChR-/MuSK-). To be eligible, patients must also have a MG-ADL score 6 (>50% non-ocular) and be on stable standard-of-care (SOC) treatment.

Senior author Heinz Wiendl, director of the Clinic of Neurology and Neurolophysiology at University Hospital Freiburg, and his colleagues will observe approximately 180 participants who are 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.

Read More: BTK Inhibitor Remibrutinib Demonstrates Positive Safety in Various Autoimmune Disorders

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 for 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 (MS) in 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 those selected, a total of 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 of 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.

Recently, Novartis received FDA approval for remibrutinib, the first and only oral Bruton’s tyrosine kinase inhibitor (BTKi) for adults with CSU who remain symptomatic despite antihistamine therapy. The twice-daily pill does not require injections or lab monitoring and 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

The FDA approval of remibrutinib is 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 remibrutinib with versus placebo achieved well-controlled disease (UAS7≤6) as early as Week 2 and at Week 12, and about 33% of patients achieved complete absence of itch and hives at Week 12. The most common adverse events (incidence ≥3%) were nasal congestion, sore throat, and runny nose (nasopharyngitis), bleeding, headache, nausea, and abdominal pain.

Referances
1. Willi R, Bril V, Howard J, et al. Relive: A Phase 3 Study Evaluating the Efficacy and Saftey of Remibrutinb in Generalized Myasthenia Gravis. Presented at resented at the 2025 American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM) Annual Meeting, held October 29-November 1, in 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. EPO-146.
3. Novartis. Novartis receives FDA approval for Rhapsido® (remibrutinib), the only oral, targeted BTKi treatment for chronic spontaneous urticaria (CSU). [Press Release]. Spetember 30, 2025. https://www.novartis.com/news/media-releases/novartis-receives-fda-approval-rhapsido-remibrutinib-only-oral-targeted-btki-treatment-chronic-spontaneous-urticaria-csu. Accessed October 31, 2025.