NeurologyLive® Year in Review 2025: Top trending Migraine Trials

The NeurologyLive® staff was busy covering clinical news and data readouts from around the world across several key neurology subspecialty areas in 2025. From major study publications and FDA decisions to societal conference sessions and expert interviews, the team spent all year bringing the latest information to the website's front page. Among the many neurology subspecialties covered, migraine research stood out in 2025, with several high-profile clinical trials delivering results that could reshape both preventive and acute treatment strategies.

Over the past 12 months, there have been several significant advances in the field of migraine, including a growing emphasis on personalized preventive strategies; expanded options for acute and long-term treatment with CGRP-targeted therapies and gepants; and the emergence of innovative nonpharmacologic approaches, such as neuromodulation devices and digital therapeutics. Researchers and clinicians have also focused on better understanding migraine subtypes, identifying biomarkers for treatment response, and addressing the broader impact of migraine on quality of life.

With the amount of ongoing research, it's nearly impossible to narrow down just 8 trials that have impacted the field of migraine research this year, but we’re highlighting some of the top ongoing trials.

Evaluating Combined Supraorbital and Occipital Neuromodulation in Resistant Migraine Trial: The RECLAIM Study

The Salvia BioElectronics PRIMUS craniofacial nerve stimulation system is designed to provide subcutaneous neurostimulation to the branches of the trigeminal and occipital nerves. Composed of a supraorbital and an occipital subcutaneous implant, the therapy is intended to modulate headache on neural networks by utilizing mild electrical pulses. Currently, the PRIMUS system is being assessed for its safety and performance among patients with resistant migraine in the RECLAIM Study (NCT06450444), a randomized, double-blind, sham-controlled trial.2

“With the RECLAIM study, we aim to demonstrate the extent to which this combined craniofacial nerve stimulation therapy—targeting both the supraorbital and occipital nerves—can provide clinical benefit to patients with resistant migraine," Wim Pollet, MD, dhief medical officer at Salvia BioElectronics, told NeurologyLive®. "The PRIMUS system (MySalvia Therapy) delivers gentle electrical pulses through two ultra-thin implants placed just beneath the skin of the head. No implanted battery is required. Patients activate the therapy using an external wearable device, which is easy to use and provides a comfortable, patient-controlled treatment."

Comparative Effectiveness of Migraine Preventive Medications: The APT Comparison Study

The APT Comparison Study (NCT06972056) is a prospective, randomized, phase 4 comparative effectiveness trial evaluating preventative migraine therapies and their effectiveness between each other. The study compares atogepant (QULIPTA®) with two established treatments, topiramate (Topamax®) and propranolol, to assess the relative efficacy and tolerability in patients with migraine. Funded by Mayo Clinic, the trial is currently recruiting and will randomly assign patients with one of the three treatment arms. In the trial, participants will record daily headache-related outcomes in an electronic headache diary over a 16-week study period.

The primary endpoint of the trial is the proportion of participants in each treatment group who both remain on their assigned medication through the first 12 weeks and achieve greater than a 50% reduction in moderate-to-severe headache days during weeks 9–12 compared with the four weeks prior to randomization. The study plans to enroll approximately 1,335 participants, with final results anticipated in 2029.

Efficacy and Safety Study of Rimegepant for the Preventative Treatment of Migraine in Pediatric Subjects

An ongoing phase 3, randomized, double-blind, placebo-controlled study (NCT05156398) sponsored by Pfizer, aims to evaluate the efficacy and safety of rimegepant (BHV3000) in migraine prevention in children and adolescents 6 to 17 years of age. Participants were randomized to receive rimegepant at a dose of 75 mg or 50 mg (two 25-mg orally disintegrating tablets) or a matching placebo. The study is currently in the recuiting phase but expected to enroll 640 participants and the completion date is marked for 2032.

The primary endpoint of this study is the change from baseline in the mean number of migraine days per month as measured over the 12-week double-blind phase of the study in adolescents with episodic migraine. Secondary endpoints include additional measures of migraine burden, treatment impact, and safety. Changes in monthly migraine days, reductions in moderate-to-severe migraine frequency, use of acute migraine-specific medications, overall tolerability, and patient-reported quality of life over the 12-week double-blind treatment phase will be recorded.

Merz’ IncobotulinumtoxinA Begins Phase 3 MINT Trials 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.1

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 migraine across 120 sites in North

Comparative Study of Oral Atogepant Versus Oral Topiramate to Assess Adverse Events in Adult Participants With Migraine (ATO-TOPIRAMATE)

Aiming to test the tolerability, safety, and efficacy of atogepant versus topiramate in subjects requiring preventive treatment of migraine, TEMPLE is an ongoing, randomized, double-blind, parallel-group, active controlled phase 3 study (NCT05748483). Sponsored by AbbVie, the trial will assign patients to receive atogepant (and placebo for topiramate) or topiramate (and placebo for atogepant) for 24 weeks. After 24 weeks, all eligible participants will receive atogepant for 52 weeks. Additionally, Participants are monitored for safety for 4 weeks after their last study treatment.

The study enrolled 545 patients and is expecting final results in May of 2026. Those enrolled must be adults with a documented history of migraine, with or without aura, for at least 12 months prior to screening. Eligible participants must also experience 4 or more migraine days per month which required preventive treatment, making them appropriate candidates for conventional migraine prophylaxis. Individuals were excluded from the study if they had previously used topiramate or atogepant, or if they had clinically significant cardiovascular, cerebrovascular, hematologic, endocrine, pulmonary, renal, hepatic, gastrointestinal, or neurologic disease.

COACT Study: CGRPmAbs + OnabotulinumtoxinA Assessment of chronic Migraine Treatments Study (COACT)

The ongoing phase 4, prospective, open-label interventional COACT study is evaluating the safety and efficacy of adding the CGRP monoclonal antibody fremanezumab (Ajovy) in patients with chronic migraine who are receiving onabotulinumtoxinA (Botox) monotherapy. The trial is sponsored by the Chicago Headache Center and Research Institute and is currently active but no longer recruiting, with 50 patients enrolled and receiving treatment.

Eligible participants must have a history of at least eight monthly migraine days and will have received at least two onabotulinumtoxinA treatments at screening. Between visit 1 (screening) and visit 3 (day 7), all patients will remain on onabotulinumtoxinA monotherapy for up to 12 weeks. Over the course of the study, participants will receive a total of two onabotulinumtoxinA treatments, administered on day 1 (visit 2) and day 90 (visit 4).

Fully Enrolled CYPRESS Phase 3 Trial to Test Ampreloxetine in Symptomatic Neurogenic Orthostatic Hypotension of MSA

An ongoing phase 3 study, dubbed CYPRESS (NCT05696717), is evaluating the efficacy and durability of ampreloxetine (Theravance Biopharma) in patients with symptomatic neurogenic orthostatic hypotension (nOH) due to multiple system atrophy (MSA). The large-scale, multicenter study enrolled 102 patients and is assessing the therapeutic potential of ampreloxetine, a once-daily, selective norepinephrine reuptake inhibitor. If successful, results from the trial are expected to fuel a new drug application (NDA) submission, coming in early 2026.1

The CYPRESS study includes a screening period, a 12-week open-label period, an 8-week randomized, double-blind withdrawal period, and a long-term extension. The primary endpoint is change from baseline in the Orthostatic Hypotension Symptom Assessment composite score, with key secondary endpoints including changes in Orthostatic Hypotension Daily Activity Scale item 1, which assesses activities requiring standing for a short time, and item 3, which assesses activities requiring short periods of walking.

Inhaled Cannabis Versus Placebo for the Acute Treatment of Migraine: a Pilot, Randomized, Double-blind, Placebo-controlled, Crossover, Dose-ranging Trial

The therapeutic potential for THC-containing cannabis as an acute treatment for migraine is being evaluated in a pilot, randomized, double-blind, placebo-controlled, crossover, dose-ranging phase 2 trial (NCT05427630). In the study, participants will treat four separate migraine attacks, each with a different intervention, using an inhaled cannabis formulation delivered via a portable device. Participants will self-administer treatment as early as possible during the course of a migraine and are instructed to take four puffs of either THC 2.5%, THC 5%, THC 10%, or placebo.

The trial is sponsored by the University of California, San Diego. Efficacy endpoints include pain freedom, pain relief, and resolution of the most bothersome symptom, as well as the presence or absence of associated symptoms such as photophobia, phonophobia, and nausea. Outcomes will be assessed at multiple time points ranging from 15 minutes to 48 hours after dosing.