Previewing Expected FDA Decisions in Neurology for 2026

Each year, the NeurologyLive^® team closely monitors the neurologic therapeutic pipeline, tracking late-stage clinical programs and regulatory milestones that have the potential to influence near-term clinical practice. As part of that effort, the team provides timely, in-depth coverage of FDA decisions that shape the evolving treatment landscape across neurologic disease states, aligning regulatory updates with expert insight on the underlying clinical trial data.

Looking ahead to the first half of 2026, several high-profile FDA decisions are expected across a range of neurologic conditions, spanning neurodegenerative disease, neuromuscular disorders, headache, epilepsy, and rare neurologic populations. These upcoming actions include anticipated approvals, regulatory verdicts on novel mechanisms, and decisions that could introduce new formulations, delivery strategies, or first-in-class options for patients with limited therapeutic alternatives.

In this feature, NeurologyLive highlights the most notable FDA decisions expected in early 2026 and why they matter for practicing neurologists. Each section outlines the regulatory context, the clinical data underpinning the decision, and the potential implications for patient care as these therapies approach key inflection points.

Tolebrutinib (Sanofi) - Non-relapsing Secondary Progressive Multiple Sclerosis

In the first half of 2026, the FDA is expected to make a decision on tolebrutinib, an investigational Bruton Tyrosine Kinase (BTK) inhibitor, under review for patients with non-relapsing secondary progressive multiple sclerosis (nrSPMS). The drug, which could potentially be the first BTK approved for nrSPMS, had its original PDUFA date pushed back twice, first in September and second in late December.¹

Unlike other MS therapies that primarily modulate peripheral immune cells, tolebrutinib is designed to inhibit BTK signaling both in the periphery and within the central nervous system, where BTK is expressed on microglia. Tolebrutinib's application is supported by data from the phase 3 HERCULES study (NCT04411641) in nrSPMS, as well as the phase 3 GEMINI 1 and 2 trials (NCT04410978; NCT04410991) of patients with relapsing MS.

Results from the HERCULES trial showed that tolebrutinib significantly delayed 6-month confirmed disability progression by 31% versus placebo (HR, 0.69; 95% CI, 0.55–0.88; P = .0026) and nearly doubled the likelihood of confirmed disability improvement (HR, 1.88; 95% CI, 1.10–3.21; P = .021). In post hoc analyses, treatment effects were greater in patients with higher baseline paramagnetic rim lesion counts, including a 54% reduction in 6-month confirmed disability worsening among those with at least 4 lesions, with similar risk reductions observed in GEMINI of 46% in patients with 1–3 lesions and 49% in those with at least 4 lesions.^2,3

GTx-104 (Grace Therapeutics) - Aneurysmal Subarachnoid Hemorrhage

The FDA is expected to make a decision on GTx-104, an injectable formulation of nimodipine, as a potential treatment for patients with aneurysmal subarachnoid hemorrhage (aSAH). GTx-104 is intended to deliver nimodipine by IV infusion using an aqueous formulation (designed for peripheral IV use), with the goal of making administration more reliable in critically ill patients who cannot swallow and reducing variability seen with oral absorption.

The drug's regulatory application was supported by results from the phase 3 STRIVE-ON study (NCT05995405), a prospective, randomized, open-label trial that compared intravenous GTx-104 with oral nimodipine in patients hospitalized with aneurysmal subarachnoid hemorrhage. The study enrolled 50 patients treated with GTx-104 and 52 patients receiving oral nimodipine and met its primary end point, demonstrating a 19% reduction in the occurrence of at least one episode of clinically significant hypotension in the GTx-104 arm compared with oral nimodipine. Patients were followed for up to 90 days, including a 21-day treatment period, allowing for assessment of both short-term safety and downstream clinical outcomes.^4,5

Despite a higher proportion of patients with the most severe aSAH (Hunt & Hess Grade V) in the GTx-104 group compared with the oral nimodipine group (8% vs 2%), outcomes favored GTx-104 across several clinically meaningful measures. Patients treated with GTx-104 experienced fewer intensive care unit readmissions, ICU days, and ventilator days. Treatment adherence also appeared improved, with 54% of patients in the GTx-104 arm achieving a relative dose intensity of at least 95% of the prescribed dose, compared with 8% in the oral nimodipine arm. Additionally, investigators observed a 29% relative increase in the proportion of patients treated with GTx-104 who achieved favorable functional outcomes at 90 days, as measured by the modified Rankin Scale.

Tavapadon (AbbVie) for Parkinson Disease

AbbVie's tavapadon, an investigational selective dopamine D1/D5 receptor partial agonist, is expected to have a decision come in the first half of 2026. Tavapadon represents a novel approach within dopaminergic therapy by preferentially targeting postsynaptic D1-like receptors in the striatum and motor cortex, with the goal of enhancing motor control while minimizing some of the complications associated with traditional dopaminergic replacement strategies.⁶

Unlike conventional therapies that primarily replace or mimic dopamine through levodopa or stimulate D2-like receptors (e.g., dopamine agonists such as pramipexole and ropinirole), tavapadon is designed to engage D1-type receptors that are directly linked to the direct basal ganglia pathway. Activation of this pathway is theorized to facilitate movement initiation and improve bradykinesia and rigidity more effectively, potentially with a favorable side effect profile regarding dyskinesia and impulse control disorders.

The application was supported by data from three randomized, placebo-controlled phase 3 trials: TEMPO-1 (NCT04201093) and TEMPO-2 (NCT04223193), which evaluated tavapadon as monotherapy in early-stage Parkinson’s disease, and TEMPO-3 (NCT04542499), which assessed tavapadon as an adjunct to levodopa in patients with motor fluctuations. Additional evidence was provided by an interim analysis from TEMPO-4 (NCT04760769), an ongoing open-label extension study.⁷

Subcutaneous Weekly Lecanemab (Eisai) Dosing for Alzheimer Disease

In 2025, the FDA approved a subcutaneous autoinjector (SC-AI) formulation of lecanemab (Leqembi; Eisai), an antiamyloid treatment, as a new method of administration for patients with early-stage Alzheimer disease (AD) or mild cognitive impairment due to AD. Weeks later, Eisai submitted supplemental biologics license application (sBLA) that would introduce a once-weekly starting dose of the SC-AI formulation for this patient population.^8,9

If approved, the Leqembi Iqlik 500 mg subcutaneous regimen, delivered as two 250 mg injections, would offer a once-weekly alternative to biweekly intravenous dosing, expanding treatment flexibility for patients and caregivers. The SC-AI formulation, which can be administered in approximately 15 seconds, would enable initiation and continuation of therapy at home and provide a choice between IV and subcutaneous administration. While current labeling requires an 18-month course of biweekly IV lecanemab before transitioning to weekly 360-mg SC-AI, the latest sBLA seeks to allow patients to begin weekly subcutaneous treatment at the start of therapy.

Tividenofusp Alfa (Denali Therapeutics) for Hunter Syndrome

On April 5, 2026, the FDA is expected to make a decision on Denali's tividenofusp alfa, an investigational agent, as the first treatment for patients with Hunter syndrome, a rare lysosomal storage disorder. The review period was originally extended after Denali submitted additional pharmacology data in response to a routine information request as part of the FDA's standard evaluation process. As part of the amendment, the FDA did not request any new efficacy, safety, or biomarker data.¹⁰

Clinical evidence supporting tividenofusp alfa includes results from a Phase 1/2 open-label study, where treatment led to substantial reductions in cerebrospinal fluid heparan sulfate (HS) — a key biomarker of disease — with mean levels falling by roughly 90 % and remaining near normal through longer follow-up, along with improvements or stabilization in adaptive behavior, cognition, hearing, and organ measurements such as liver volume. Early data also showed reductions in neurofilament light, a marker of neuronal injury, suggesting potential impact on neurodegeneration. A Phase 2/3 COMPASS study is ongoing, randomizing patients to tividenofusp alfa versus idursulfase to further evaluate efficacy and safety.^11,12

REFERENCES
1. Sanofi provides update on tolebrutinib in primary progressive multiple sclerosis. Sanofi. News release. December 15, 2025. Accessed December 18, 2025. https://www.sanofi.com/assets/dotcom/pressreleases/2025/2025-12-15-06-05-00-3205094-en.pdf
2. Fox RJ, Bar-Or A, Traboulsee A, et al. Efficacy and safety of tolebrutinib versus placebo in non-relapsing secondary progressive multiple sclerosis: results from the Phase 3 HERCULES Trial. Presented at: 2024 ECTRIMS; September 18-20, 2024; Copenhagen, Denmark. Abstract 4027.
3. Oh J, Fox RJ, Arnold DL, et al. LB1.1. Paramagnetic rim Lesions as a prognostic and predictive biomarker in the tolebrutinib phase 3 trials for disability outcomes. Presented at: 2025 ACTRIMS Forum; February 27-March 1, 2025; West Palm Beach, FL. Abstract LB1.1
4. Grace Therapeutics Announces Submission of New Drug Application to U.S. Food and Drug Administration for GTx-104. News release. June 25, 2025. Accessed December 18, 2025. https://www.globenewswire.com/news-release/2025/06/25/3105015/0/en/Grace-Therapeutics-Announces-Submission-of-New-Drug-Application-to-U-S-Food-and-Drug-Administration-for-GTx-104.html
5. Grace Therapeutics Announces Results From Pivotal Phase 3 STRIVE-ON Safety Trial of GTx-104 in aSAH. News release. Grace Therapeutics. February 10, 2025. Accessed December 18, 2025. https://www.gracetx.com/investors/news-events/press-releases/detail/282/grace-therapeutics-announces-results-from-pivotal-phase-3-strive-on-safety-trial-of-gtx-104-in-asah
6. AbbVie Submits New Drug Application to U.S. FDA for Tavapadon for the Treatment of Parkinson's Disease. September 26, 2025. Accessed December 18, 2025. http://news.abbvie.com/2025-09-26-AbbVie-Submits-New-Drug-Application-to-U-S-FDA-for-Tavapadon-for-the-Treatment-of-Parkinsons-Disease
7. Cerevel Therapeutics announces positive topline results for tavapadon in phase 3 adjunctive trial for people living with Parkinson disease. Cerevel Therapeutics. April 18, 2024. Accessed December 18, 2025. https://www.globenewswire.com/news-release/2024/04/18/2865216/0/en/Cerevel-Therapeutics-Announces-Positive-Topline-Results-for-Tavapadon-in-Phase-3-Adjunctive-Trial-for-People-Living-with-Parkinson-s-Disease.html
8. FDA Approves LEQEMBI® IQLIK™ (lecanemab-irmb) Subcutaneous Injection for Maintenance Dosing for the Treatment of Early Alzheimer's Disease. News release. August 29, 2025. Accessed December 18, 2025. https://www.prnewswire.com/news-releases/fda-approves-leqembi-iqlik-lecanemab-irmb-subcutaneous-injection-for-maintenance-dosing-for-the-treatment-of-early-alzheimers-disease-302542371.html
9. Eisai Initiated Rolling Supplemental Biologics License Application to the U.S. FDA for LEQEMBI® IQLIKTM (lecanemab-irmb) as a Subcutaneous Starting Dose for the Treatment of Early Alzheimer’s Disease Under Fast Track Status. News release. Eisai. September 3, 2025. Accessed December 18, 2025.
10. Denali Therapeutics announces FDA review extension of BLA for tividenofusp alfa for the treatment of MPS II (Hunter syndrome). News release. Denali Therapeutics. October 13, 2025. Accessed December 18, 2025. https://www.globenewswire.com/news-release/2025/10/13/3165786/0/en/Denali-Therapeutics-Announces-FDA-Review-Extension-of-BLA-for-Tividenofusp-Alfa-for-the-Treatment-of-MPS-II-Hunter-Syndrome.html
11. Denali Therapeutics announces primary analysis and long-term follow-up of phase 1/2 study in Hunter syndrome (MPS II) with tividenofusp alfa. News release. Denali Therapeutics. February 6, 2025. Accessed December 18, 2025. https://www.globenewswire.com/news-release/2025/02/06/3022238/0/en/Denali-Therapeutics-Announces-Primary-Analysis-and-Long-Term-Follow-Up-of-Phase-1-2-Study-in-Hunter-Syndrome-MPS-II-with-Tividenofusp-Alfa.html
12. A study to determine the efficacy and safety of tividenofusp alfa (DNL310) vs idursulfase in pediatric and young adult participants with neuronopathic (nMPS II) or non-neuronopathic mucopolysaccharidosis type II (nnMPS II) (COMPASS). Clinicaltrials.gov. Updated August 5, 2025. Accessed December 18, 2025.