NeurologyLive® Year in Review 2025: Notable Trials Beginning This Year

The NeurologyLive® staff spent 2025 covering a wide range of clinical news and data readouts from around the world, spanning multiple subspecialties within neurology. From major study publications and FDA regulatory decisions to key sessions at scientific meetings and in-depth expert interviews, the team remained focused on delivering timely, relevant updates to the website’s front page throughout the year. Across the diverse areas of neurology covered, clinical research continued to drive meaningful shifts in how neurological diseases are understood, studied, and treated.

Over the past 12 months, significant advances have emerged across the field of neurology, including a growing emphasis on precision and personalized approaches to care; expanded therapeutic options across both disease-modifying and symptomatic treatments; and continued innovation in nonpharmacologic strategies such as neuromodulation, digital health technologies, and biomarkers to guide treatment decisions. Investigators have also placed increased focus on disease heterogeneity, earlier diagnosis, and the broader impact of neurological conditions on long-term outcomes and quality of life.

With the amount of ongoing research, it's nearly impossible to narrow down just 7 trials that have impacted the field of neurology this year, but we’re highlighting some of the top ongoing trials.

Phase 4 Study Testing Transition of Anti-CD20 to Ozanimod in Stable MS

A recently launched phase 4, open-label, prospective study (NCT06529406) will test the safety and efficacy of ozanimod (Zeposia; BMS), an FDA-approved sphingosine 1-phosphate receptor (S1P) modulator, as a de-escalation therapy in clinically stable patients with relapsing multiple sclerosis (MS) previously treated with anti-CD20 medication. The study will use new T2 lesion count and number of serious infections over at least 36 months of follow up as the primary end points.¹ Adverse events (AEs), number of infections, immunoglobulin G and IgM levels, number of relapses, and no evidence of disease activity (NEDA-3) will be used as secondary end points.

The study, conducted across several tertiary MS referral centers, is expected to include at least 500 patients with MS-related symptoms for at least 3 years who’ve had no inflammatory disease activity for at least 2 years and were on anti-CD20 therapy continuously for at least 2 years. Study site start-up is currently in progress, with the hope that the findings will provide valuable clinical insights on treatment decisions for stable patients living with the disease.

Phase 4 ENABLE Trial Assesses Real-World Efficacy of Ublituximab in Relapsing Multiple Sclerosis

Investigators shared the study design of ENABLE, the first phase 4, post-marketing observational trial (NCT06433752) assessing real-world efficacy and safety of ublituximab (Briumvi; TG Therapeutics), one of the more newly approved medications for relapsing MS that came into market in 2022. The study, which aims to collect data on effectiveness, safety, and tolerability of the therapy, is expected to enroll at least 500 patients with relapsing MS across 100 centers in the United States.²

Expected to span a total of 96 weeks, this phase 4 study will use annualized relapse rates (ARRs) as the primary end point, with secondary end points that include proportion of patients experiencing AEs, as well as incidence, severity, and type of infusion-related reactions (IRRs) at each infusion. Intended to collect data on a wide range of geographic and racial/ethnic populations, enrollment for the study is expected to take up to 24 months, with several sites already beginning enrollment back in mid-2024.

Phase 3 MINT Trials of IncobotulinumtoxinA for Migraine Prevention

Patient dosing has begun for 2 new, large-scale, phase 3 trials, dubbed MINT-E (NCT07018700) and MINT-C (NCT07018713), that test the therapeutic safety and efficacy of incobotulinumtoxinA (Xeomin; Merz Therapeutics) as an option for episodic and chronic migraine in adults.³ IncobotulinumtoxinA is a purified formulation of botulinum toxin type A used to treat a range of neurologic and movement-related disorders, as well as certain non-neurologic conditions.

Each of these trials will include the opposite patient population, with MINT-E comprising those with episodic migraine, defined as less than 15 headache days per month, while MINT-C includes those with chronic migraine. The studies, which are currently enrolling, are expected to include 1770 adults with migraines across 120 sites in North America and Europe.

Phase 3 BRAVE Study of Omaveloxolone in Pediatric Friedreich Ataxia

Biogen initiated a new phase 3 trial dubbed BRAVE (NCT06953583) that tests the therapeutic potential of omaveloxolone (Skyclarys), the only FDA-approved therapy for adults with Friedreich ataxia (FA), in pediatric patients living with the disease. The 52-week trial will include 255 children with FA, both non-ambulatory and ambulatory, testing efficacy, safety, pharmacokinetics and pharmacodynamics of the approved therapy.^4,5

The newly initiated study, split into 2 parts, includes children with genetically confirmed FA aged 2 to 16 who will receive either omaveloxolone once a day (QD) or placebo. Part 1, the randomized controlled portion, uses change in Upright Stability Score (USS), a part of the validated modified FA Rating Scale (mFARS), as the primary end point. Part 2, or the open-label extension phase, lasts up to 104 weeks, giving patients from either cohort the opportunity to experience omaveloxolone treatment.

Phase 3 Study of 1st Generation Antihistamine EPX-100 in Lennox-Gastaut Syndrome

A new phase 3 study (NCT05066217) will test the efficacy and safety of EPX-100 (Harmony Biosciences), a 1st generation antihistamine agent, as a potential treatment for patients with Lennox-Gastaut syndrome (LGS), a rare epileptic disorder. Overall, the study will enroll patients aged at least 2 years old with LGS who will be followed for a 20-week period, with optional open-label extension after the end of the maintenance phase.⁶ Eligible patients must have onset of seizures before age 11, current countable seizures leading to falls or drops, and an inadequate response to antiseizure medications.

The study design includes a 4-week observation phase, 4-week titration phase, and 12-week maintenance phase to test EPX-100. The trial, which includes those with at least 4 countable major motor seizures, will use percentage change in CMMS-28 from baseline through the end of the double-blind period as the primary end point. Safety assessments will include incidence and severity of AEs and clinical laboratory tests.

POLARIS-AD Trial Assessing Oral Therapy AR1001 for Early Alzheimer Disease

POLARIS-AD is an ongoing phase 3 global, multicenter, double-blind, placebo-controlled, 52-week treatment parallel group trial (NCT05531526) evaluating the safety and efficacy of AR1001 (mirodenafil), a novel oral therapy targeting toxic amyloid-beta oligomers, in patients with mild cognitive impairment (MCI) or mild dementia due to Alzheimer disease (AD). The trial, a large-scale study of more than 1500 patients, is expected to have topline results readout in 2026.⁷

Baseline demographics and characteristics of the trial participants include a Clinical Dementia Rating-Sum of Boxes (CDR-SB) mean score, the primary end point, of 3.45 (±1.70). On other secondary outcomes, such as Alzheimer’s Disease Assessment Scale – Cognitive Subscale, 13-item (ADAS-Cog13), patients had a baseline score of 27.75 (±8.02). Continued data showed that at baseline, patients had Amsterdam Instrumental Activities of Daily Living Questionnaire (A-IADL) score of 72 (±20.72), Geriatric Depression Scale (GDS) score of 1.6 (±1.81), and a Mini-Mental State Evaluation (MMSE) score of 24.01 (±2.70).

ADDRESS-LC Trial Evaluating Bezisterim as Treatment for Neurological Symptoms of Long COVID

Earlier this year, BioVie had its first patients dosed in a randomized, placebo-controlled, phase 2 study, dubbed ADDRESS-LC (NCT06847191) that tests the therapeutic potential of bezisterim, a blood brain barrier-permeable, insulin-sensitizer, as a treatment for neurological symptoms associated with Long COVID. The newly initiated study consists of 200 patients with Long COVID who have cognitive impairment sequelae and fatigue for at least 3 months.⁸

ADDRESS-LC includes those aged 18 to 64 years of age who are willing to allow blood collection and are able to pass all screening tests and procedures. The study excludes those who have received a COVID-19 vaccination within 30 days, had previous admission to an intensive care unit for COVID-19, or had a medical history of major mental or physical illness prior to COVID-19 infection. Funded by a grant from the Department of Defense, the study assigns patients to either bezisterim or placebo twice daily for 84 days, using change in performance on the Cogstate Cognition battery as the primary outcome measure. Initial data from the trial is expected to be released in the first half of 2026.

REFERENCES
1. Alvarez E, Honce J, Chaudry B, et al. P111. Trial in Progress: A Multicenter, Open-Label, Prospective Phase 4 Study Evaluating the Safety and Efficacy of Sequencing From Anti-CD20 Therapies to Ozanimod in Clinically Stable Patients With Multiple Sclerosis. Presented at: 2025 ACTRIMS Forum; Feb 27-March 1; West Palm Beach, FL. ABSTRACT P111.
2. Fox E, Parker J, Bodhinathan K, Sportelli P, Miskin H, Hersh C. ENABLE: The First Phase 4 Observational Study for Patients with Relapsing MS Treated with Ublituximab in Real World Clinical Setting. Presented at: 2025 AAN Annual Meeting; April 5-9; San Diego, CA. ABSTRACT 004773
3. Merz Therapeutics Announces First Patients Enrolled in Two Phase III Trials Investigating XEOMIN® (incobotulinumtoxinA) for Migraine Prevention. News release. Merz Therapeutics. August 25, 2025. Accessed August 26, 2025. https://www.businesswire.com/news/home/20250822411240/en/Merz-Therapeutics-Announces-First-Patients-Enrolled-in-Two-Phase-III-Trials-Investigating-XEOMIN-incobotulinumtoxinA-for-Migraine-Prevention
4. Biogen Initiates Phase 3 Pediatric Study of Omaveloxolone for the Treatment of Friedreich Ataxia. News release. June 18, 2025. Accessed June 18, 2025. https://investors.biogen.com/news-releases/news-release-details/biogen-initiates-phase-3-pediatric-study-omaveloxolone-treatment
5. A Study to Learn More About the Effects and Long-Term Safety of BIIB141 (Omaveloxolone) in Participants With Friedreich's Ataxia Aged 2 to 15 Years Old. Clinicaltrials.gov. Updated June 17, 2025. Accessed June 18, 2025. https://clinicaltrials.gov/study/NCT06953583
6. Ray A, Nomikos G, Runyan G, et al. A 20-Week Multicenter, Randomized, Double-Blind (DB), Placebo-Controlled, Phase 3 Trial (EPX 100-003) of EPX-100 (Clemizole Hydrochloride) as Adjunctive Therapy in patients with Lennox-Gastaut Syndrome (LGS). Presented at: 2025 AAN Annual Meeting; April 5-9; San Diego, CA. ABSTRACT 003976
7. Prins N, Atri A, Melgar-Somoza F, et al. POLARIS-AD: Global Enrollment in the Largest Phase 3 Trial of an Oral Multi-Mechanistic PDE5 Inhibitor for Early AD Using Biomarker-Agnostic Modalities for Amyloid Confirmation. Presented at: Clinical Trials on Alzheimer’s Disease Conference (CTAD); December 1-4; San Diego, California
8. BioVie Enrolls First Patient in ADDRESS-LC Clinical Trial Assessing Novel Anti-Inflammatory Candidate Bezisterim for the Treatment of Neurological Symptoms Associated with Long COVID. News release. BioVie. May 15, 2025. Accessed May 22, 2025. https://investors.bioviepharma.com/news/news-details/2025/BioVie-Enrolls-First-Patient-in-ADDRESS-LC-Clinical-Trial-Assessing-Novel-Anti-Inflammatory-Candidate-Bezisterim-for-the-Treatment-of-Neurological-Symptoms-Associated-with-Long-COVID/default.aspx