Phase 3b RESHAPE Study Evaluates Risk–Benefit of Switching From Ocrelizumab to BTK Inhibitor Remibrutinib

At the 2026 Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) Forum, held February 5-7, in San Diego, California, researchers presented the study design for an ongoing global phase 3b RESHAPE trial (NCT06846281) testing the benefit-risk profile of remibrutinib, a Bruton’s tyrosine kinase (BTK) inhibitor, in patients with relapsing multiple sclerosis (RMS) who transition from ocrelizumab versus those who continue treatment with ocrelizumab.¹

RESHAPE, which spans roughly 20 countries, will be enrolling approximately 360 participants to be randomized 1:1 to either switch to remibrutinib or continue ocrelizumab, with about 180 individuals assigned to each treatment arm. Eligible participants are adults aged 40 to 70 years with RMS who are receiving ocrelizumab at standard doses in routine clinical practice, are neurologically stable in 30 days prior to randomization, and are considered suitable for switching to remibrutinib based on physician judgment or patient preference.

“This [study] design directly addresses the real-world clinical question of whether patients doing well on anti-CD20 therapy might benefit from switching to a BTK inhibitor, which is particularly relevant for older people living with MS who have accumulating concerns about prolonged B-cell depletion and infection risks,” Carrie Hersh, DO, MSc, FAAN, associate professor of neurology at Cleveland Clinic Lerner College of Medicine, told NeurologyLive^®. “The concept is intriguing because it tests whether you can step away from complete B-cell depletion to selective BTK inhibition while maintaining disease control. Essentially, we are interested to witness if remibrutinib can ‘hold the line’ established by ocrelizumab with a potentially safer long-term profile, particularly important for aging patients where cumulative immunosuppression and infection risk become increasingly concerning.”

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In the trial, participants randomized to the investigational arm will receive remibrutinib at a dose of 100 mg orally twice daily. Those assigned to the comparator arm will continue ocrelizumab at approved dosing schedules of 600 mg administered intravenously or 920 mg administered subcutaneously every 6 months. Investigators noted that the study will include a 24-month core treatment period, followed by an extension phase of up to an additional 24 months during which all participants will receive remibrutinib.

In the study, the primary efficacy end point will be annualized rate of new or enlarging T2 lesions at 24 months compared with baseline. Other key secondary endpoint include the proportion of participants achieving no evidence of disease activity-3 from baseline to 24 months, with additional secondary efficacy and safety outcomes also evaluated. Overall, the study aims to provide comparative scientific evidence regarding the benefit–risk profile of remibrutinib in patients with RMS transitioning from ocrelizumab compared with those who remain on ocrelizumab.

“I think this [BTK inhibitor] class represents a promising therapeutic advancement for MS because it offers a potential ‘sweet spot’ between efficacy and safety, targeting pathogenic B-cell function and microglial activation without complete B-cell depletion, which theoretically can reduce infection risk while maintaining disease control,” Hersh, who is also president-elect of the Consortium of Multiple Sclerosis Centers (CMSC), said to NeurologyLive. “The key questions are whether CNS-penetrant BTK inhibition can meaningful impact compartmentalized chronic active inflammation and slow disability independent of relapses in the long-term (something we haven't definitively shown yet with other oral therapy classes), and whether the safety profile truly proves superior to anti-CD20 therapies in long-term use.”

Remibrutinib is also being investigated in the randomized, double-blind, placebo-controlled phase 3 RELIEVE study (NCT06744920) in patients with general myasthenia gravis (gMG).² The study design, presented at the 2025 American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM) meeting, held October 29 to November 1, in San Francisco, California, enrolls patients aged 18 to 75 years diagnosed with gMG and are either acetylcholine receptor positive, muscle-specific tyrosine kinase positive, or double-seronegative. The 6-month trial will assess the change in myasthenia gravis activities of daily living score (MG-ADL) total score, the primary outcome, from baseline to 6 months.

Click here for coverage of 2026 ACTRIMS Forum.

REFERENCES
1. Hersh CM, Oreja-Guevara C, de Seze J, et al. Efficacy and Safety of Remibrutinib After Switching From Ocrelizumab in Participants With Relapsing Multiple Sclerosis: RESHAPE Study Design. Presented at ACTRIMS Forum 2026; February 5-7; San Diego, California. P113.
2. 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.