Research News
By Tom Garry and Susan Wells Courtney
Reviewed by Dr. Barry A. Hendin, MSAA’s Chief Medical Officer
Remibrutinib Shows Positive Results from Two Phase III Studies
On September 1, 2026, positive results were announced from two Phase III studies of the investigational medication, remibrutinib, in individuals with relapsing forms of MS. These two international Phase III trials, REMODEL-1 and REMODEL-2, were identical in design and together enrolled approximately 2,000 adult participants.1
These studies were multicenter, randomized, and double-blinded – comparing the effectiveness and safety of remibrutinib to teriflunomide (Aubagio®) – for a period of up to 30 months (two-and-a half years). After the 30-month period was complete, the studies continued as open-label extensions for up to five years. To clarify, in a double-blind study, neither the participants nor the medical team know who is receiving the medication and who is receiving the placebo. In an open-label study, both the participants and the medical team are aware of what each individual is receiving.
Remibrutinib is an experimental oral disease-modifying therapy (DMT) belonging to a class of medications known as Bruton’s tyrosine kinase inhibitors, or BTKi’s. These medications modulate both B-cells and myeloid cells – such as microglia and macrophages – which play important roles in immune function and can contribute to the development of MS. BTKi medications cross the blood-brain barrier, enabling them to impact chronic inflammation within the central nervous system (CNS). The CNS is comprised of the brain, spinal cord, and optic nerves.
In both studies, compared to teriflunomide, remibrutinib significantly reduced annualized relapse rate (ARR), which was a primary endpoint. Remibrutinib also showed positive results in all of the secondary endpoints, which included: a delay in confirmed disability progression at both three and six months; a reduction in CNS lesions as shown on magnetic resonance imaging (MRI); lower serum neurofilament light chain concentrations, indicating less CNS nerve damage; and a higher proportion of participants with no evidence of disease activity (NEDA).
The US Food and Drug Administration (FDA) approved remibrutinib (with the brand name, “Rhapsido®”) in September 2025 for the treatment of chronic spontaneous urticaria (CSU), a condition exhibiting chronic hives with no known external trigger. In the REMODEL-1 and REMODEL-2 Phase III trials for individuals with relapsing MS, the safety profile was positive, consistent with remibrutinib in CSU, with no liver safety signal.
FDA Approves Ocrevus® for Pediatric Relapsing-Remitting MS
In May 2026, the Food and Drug Administration (FDA) approved Ocrevus® (ocrelizumab) for the treatment of relapsing-remitting MS in children and adolescents age 10 and older who weigh 55 pounds or more.2 The approval makes the intravenously infused medication only the second disease-modifying therapy (DMT) with an FDA-sanctioned indication for use in pediatric patients.
In 2018, the FDA approved Gilenya® (fingolimod) for use in children and adolescents ages 10 to 17 years who have relapsing forms of MS.
In the Phase III OPERETTA 2 study, ocrelizumab cut annualized relapse rate 48% vs fingolimod (0.07 vs 0.14). Ocrelizumab also reduced new or enlarging T2 lesions (48% reduction vs fingolimod) and gadolinium-enhancing T1 lesions (87% reduction vs fingolimod). In addition, safety in children was similar to the safety in adults, with infrequent serious adverse events and infections, and no discontinuations resulting from adverse events.
Studies Demonstrate Favorable Outcomes with Fenebrutinib for Both Relapsing and Primary-Progressive MS
Fenebrutinib is an investigational, oral disease-modifying therapy (DMT) belonging to a class of medications known as Bruton’s tyrosine kinase inhibitors, or BTKi’s. As noted earlier, these medications modulate both B-cells and myeloid cells – such as microglia and macrophages – which play important roles in immune function and can contribute to the development of MS. BTKi medications cross the blood-brain barrier, enabling them to impact chronic inflammation in the central nervous system.
Involving almost 1,500 people with relapsing MS,3 FENhance 1 and FENhance 2 are similarly designed Phase III studies being conducted to evaluate the safety and efficacy of fenebrutinib versus Aubagio® (teriflunomide) in people with relapsing MS. In these two studies, the relapse rate for those taking fenebrutinib was between 40% and 50% lower than for those taking Aubagio. In addition, significant relative reductions in T1 gadolinium-enhancing lesions and new or enlarging T2 lesions were seen on MRI with fenebrutinib compared to Aubagio.
Moving from relapsing MS to primary-progressive MS (PPMS), the Phase III FENtrepid trial assessed the efficacy and safety of fenebrutinib compared to Ocrevus® (ocrelizumab) in 985 people with PPMS. Ocrevus is an intravenously infused medication that is currently the only disease-modifying therapy (DMT) approved for the treatment of PPMS. In the study, fenebrutinib had a 12% reduction in risk of disability progression compared to Ocrevus.4
On September 29, 2026, the company developing fenebrutinib announced that the US Food and Drug Administration (FDA) has accepted their New Drug Application (NDA) under priority review of fenebrutinib for the treatment of both relapsing and primary-progressive forms of MS.
Medical details and study results provided in MSAA’s published materials are for informational purposes only and are not to be considered as treatment advice or recommendations. Readers are encouraged to consult a healthcare professional before making any changes to their current treatment regimen.
References
1. Ciccone I, Remibrutinib Meets Primary End Point in Phase 3 REMODEL Trials for Relapsing Multiple Sclerosis. NeurologyLive. September 1, 2026.
2. Brooks M, FDA Approves Ocrelizumab for Pediatric Relapsing MS. Medscape. May 11, 2026. FDA Approves Ocrelizumab for Pediatric Relapsing MS.
3. Oh J, Bar-Or A, Giovannoni G, et al. Efficacy and safety of fenebrutinib vs teriflunomide in relapsing multiple sclerosis: results of the FENhance 1 and 2 studies. LBA01. Consortium of Multiple Sclerosis Centers 2026 Annual Meeting, May 27-30, 2026, Charlotte, North Carolina.
4. Bar-Or A, Oh J, Giovannoni G, et al. Efficacy and safety of fenebrutinib vs ocrelizumab in primary progressive multiple sclerosis: primary results of the Phase III FENtrepid Study. DMT06. Consortium of Multiple Sclerosis Centers 2026 Annual Meeting, May 27-30, 2026, Charlotte, North Carolina.