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Introduction

Advances in neurology therapeutics continue to accelerate across diverse disease areas. In 2026, several novel agents and approaches – ranging from orexin receptor agonists in narcolepsy to immunomodulatory strategies in multiple sclerosis (MS), precision anticoagulants in stroke prevention, and innovative formulations in acute neurovascular care – are poised to reshape clinical practice. This review highlights key breakthroughs and pivotal trial readouts anticipated this year.

Orexin agonists in narcolepsy

One neurology milestone to watch in 2026 is the emergence of orexin agonists for narcolepsy, a therapeutic approach that targets the underlying loss of orexin signaling rather than treating symptoms alone. Oveporexton (TAK-861), a first-in-class, oral orexin receptor 2 (OX2R)-selective agonist, reported landmark Phase III results in narcolepsy type 1 (NT1) at the World Sleep Congress 2025. Both the FirstLight (NCT06470828) and RadiantLight (NCT06505031) trials met all primary and secondary endpoints, demonstrating broad, clinically meaningful improvements in wakefulness, cataplexy, and quality of life.1 Based on these results, oveporexton is on track for U.S. Food and Drug Administration (FDA) submission by the end of March 2026.2

Another agent, alixorexton (ALKS 2680), has been granted Breakthrough Therapy designation by the FDA for the treatment of NT1 supported by data from the Phase II Vibrance-1 trial (NCT06358950). There are plans for a global Phase III program in the first quarter of 2026.3 Data from a Phase Ib trial (NCT06462404) of the OX2R agonist E2086 were also presented at the 2025 World Sleep Congress, demonstrating the potential to improve daytime wakefulness in individuals with NT1.4

BTK inhibitors in MS

Bruton’s tyrosine kinase (BTK) inhibitors represent a promising new approach in MS by selectively modulating B-cells and innate immune cells such as microglia and macrophages, with the potential to address both peripheral immune activation and chronic central nervous system inflammation that drive disease progression.5 Tolebrutinib has been the most advanced agent in this space, with Phase III data suggesting an ability to slow disability accumulation, an area of large unmet medical need, particularly in non-relapsing secondary progressive MS (nrSPMS). However, in December 2025, the FDA issued a complete response letter declining approval of tolebrutinib for nrSPMS, despite prior Breakthrough Therapy designation and positive disability outcomes in the HERCULES trial (NCT04411641). While this decision represents a setback in the field, regulatory reviews continue in Europe and other regions, and ongoing engagement with the FDA aims to define a path forward.6,7

Fenebrutinib is also being explored in the FENhance 1 (NCT04586010) and FENhance 2 (NCT04586023) trials for relapsing MS, and the FENtrepid trial (NCT04544449) for primary progressive MS. FENhance 2 met its primary endpoint, showing fenebrutinib significantly reduced relapses compared with teriflunomide. The results from FENhance 1 are expected in the first half of 2026.8

CAR T-cells in MS

There are several early-stage trials evaluating the safety and efficacy of CAR T-cell therapy in refractory progressive forms of MS, including the Phase I BOBCAT (AUTO1-MS1; NCT07139743) trial in the UK. This study plans to recruit 18 people between the ages of 18 and 60 to receive obecabtagene autoleucel (obe-cel), with the first patient already having received the treatment.9,10 Another agent, KYV-101, had successful Phase I findings (NCT06138132) and plans to move forward to a Phase II trial (KYSA-7; NCT06384976).11

“On one hand the mechanism of CAR-T suggests potential in multiple sclerosis and great potential perhaps…given central nervous system penetration. But at the same time, there are risks that remain undefined.” – Jeffrey Dunn, MD, Stanford University School of Medicine, Palo Alto, CA.

Factor XIa inhibitors in secondary stroke prevention

Factor XIa (FXIa) inhibition is emerging as a promising strategy for secondary stroke prevention, aiming to reduce thrombosis while minimizing bleeding risk. The Phase III OCEANIC-STROKE trial (NCT05686070) of asundexian met its primary efficacy and safety endpoints, with detailed results being presented at an upcoming conference.12

We spoke with Ashkan Shoamanesh, MD, McMaster University, Population Health Research Institute, Hamilton, Canada, at the 2025 World Stroke Congress on the current status of trials investigating FXIa inhibitors, including OCEANIC-STROKE and the LIBREXIA-STROK trial (NCT05702034) of milvexian. Data from LIBREXIA-STROK is expected in 2026.13

GTx-104 for aneurysmal subarachnoid hemorrhage (aSAH)

GTx-104 is an intravenous (IV) formulation of nimodipine for aSAH, with an FDA Prescription Drug User Fee Act (PDUFA) target date of April 23, 2026. The New Drug Application (NDA) is supported by the Phase III STRIVE-ON trial (NCT05995405), a prospective, randomized, open-label study comparing GTx-104 with oral nimodipine in patients hospitalized with aSAH. STRIVE-ON met its primary endpoint, showing fewer hypotensive episodes with GTx-104, alongside higher relative dose intensity and favorable functional outcomes.14

Efgartigimod for myasthenia gravis

In January 2026, the FDA accepted for priority review a supplemental Biologics License Application (sBLA) for efgartigimod for the treatment of adults with acetylcholine receptor antibody (AChR-Ab) seronegative generalized myasthenia gravis (gMG), with a PDUFA target action date of May 10, 2026. This is supported by the randomized, double-blind, placebo-controlled, multi-center Phase III ADAPT SERON trial (NCT06298552). This study met its primary endpoint, demonstrating a statistically significant improvement in Myasthenia Gravis Activities of Daily Living (MG-ADL) total score compared with placebo after four weeks. This represents a significant step forward in addressing the unmet treatment need for patients with AChR-Ab seronegative gMG.15

Conclusion

With several pivotal trial readouts and regulatory decisions expected in 2026, neurology is entering a period of meaningful clinical change. Advances ranging from orexin agonists in narcolepsy to immunomodulatory and cellular approaches in MS, alongside innovations in stroke prevention and acute neurovascular care, signal a shift toward more targeted and effective therapies. For clinicians, staying abreast of these developments will be essential as new data begin to shape future standards of care across multiple neurological diseases.

References

  1. Takeda. Takeda Presents Orexin Data from Landmark Oveporexton (TAK-861) Phase 3 Program in Narcolepsy Type 1 at World Sleep 2025. Available here. (Last accessed 01/21/2026).
  2. Patient-Centered Outcomes Research Institute. Oveporexton (TAK-861) to treat narcolepsy type 1. Available here. (Last accessed 01/21/2026).
  3. Alkermes. Alixorexton Granted Breakthrough Therapy Designation by U.S. FDA for the Treatment of Narcolepsy Type 1. Available here. (Last accessed 01/21/2026).
  4. Eisai. Eisai Presents Clinical Study Results of Novel Orexin Receptor Agonist E2086 for Narcolepsy at World Sleep 2025. Available here. (Last accessed 01/21/2026).
  5. Airas L, Bermel RA, Chitnis T, et al. A review of Bruton’s tyrosine kinase inhibitors in multiple sclerosis. Ther Adv Neurol Disord. 2024 Apr 17;17:17562864241233041.
  6. Sanofi. Press Release: Sanofi provides update on tolebrutinib regulatory submission in non-relapsing secondary progressive multiple sclerosis. Available here. (Last accessed 01/22/2026).
  7. Sanofi. Press Release: Tolebrutinib meets primary endpoint in HERCULES phase 3 study, the first and only to show reduction in disability accumulation in non-relapsing secondary progressive multiple sclerosis. Available here. (Last accessed 01/22/2026).
  8. Roche. Roche’s fenebrutinib shows unprecedented positive Phase III results as the potential first and only BTK inhibitor in both relapsing and primary progressive multiple sclerosis. Available here. (Last accessed 01/22/2026).
  9. University College London Hospitals. First UK patient with multiple sclerosis trialling CAR T cell therapy at UCLH. Available here. (Last accessed 01/22/2026)
  10. MS Trust. UK trial begins for CAR-T therapy in MS. Available here. (Last accessed 01/22/2026).
  11. Kyverna Therapeutics. Kyverna’s KYV-101 Receives U.S. FDA Clearance for Treatment of Patients With Refractory, Progressive Multiple Sclerosis in the KYSA-7 Phase 2 Trial. Available here. (Last accessed 01/22/2026).
  12. Bayer. Bayer’s Asundexian Met Primary Efficacy and Safety Endpoints in Landmark Phase III OCEANIC-STROKE Study in Secondary Stroke Prevention. Available here. (Last accessed 01/22/2026).
  13. Bristol Myers Squibb. Update on Phase 3 Librexia ACS Trial. Available here. (Last accessed 01/22/2026).
  14. Grace Therapeutics. Grace Therapeutics Announces U.S. Food and Drug Administration Acceptance for Review of New Drug Application for GTx-104. Available here. (Last accessed 01/22/2026).
  15. Argenx. argenx Announces FDA Acceptance of Supplemental Biologics License Application with Priority Review for VYVGART in AChR-Ab Seronegative gMG. Available here. (Last accessed 01/22/2026).
Written by Hannah Elkheir
Reviewed by Thomas Southgate
Publishing date: 28 January, 2026
The content of VJNeurology is intended for healthcare professionals