Fremanezumab-vfrm (AJOVY) reduces migraine frequency in children, adolescents with episodic migraine

Fremanezumab-vfrm (AJOVY; Teva), a monoclonal antibody targeting calcitonin gene–related peptide (CGRP), significantly reduced migraine frequency compared with placebo in children and adolescents with episodic migraine, according to phase 3 data from the SPACE trial published in The New England Journal of Medicine.^1,2

The findings supported the FDA’s approval of fremanezumab for the preventive treatment of episodic migraine in pediatric patients aged 6 to 17 years who weigh 45 kg or more.³

Teva Pharmaceuticals announced the publication of the SPACE trial results, noting that the approval makes fremanezumab the first CGRP antagonist indicated for preventive treatment of episodic migraine in pediatric patients. In a statement accompanying the announcement, Eric Hughes, MD, PhD, executive vice president of global R&D and chief medical officer at Teva, said, “With an estimated 1 in 10 children and adolescents in the U.S. living with migraine, the need for effective preventive options is critical as this condition can disrupt daily life for patients and families.” He added, “The SPACE trial results published in the New England Journal of Medicine add to the growing body of evidence supporting AJOVY and build on its established use in adults. Teva is proud to be leading the charge and continuing to innovate for the migraine community.”

Trial design and population

SPACE was a multicenter, randomized, double-blind, placebo-controlled, parallel-group phase 3 trial that enrolled 237 children and adolescents aged 6 to 17 years with episodic migraine, defined as migraine for at least 6 months and a history of 14 or fewer headache days per month. Participants were required to have at least 4 headache days per month during the 3 months before screening. The trial was conducted at 89 sites across nine countries between August 2020 and March 2024.

After a 28-day baseline period, participants were randomized in a 1:1 ratio to receive monthly subcutaneous fremanezumab or a matched placebo for 3 months. Dosing was weight-based: patients weighing less than 45 kg received 120 mg, and those weighing 45 kg or more received 225 mg. Use of acute migraine medications was permitted, and up to 30% of participants could continue stable doses of up to two preventive migraine medications.

The primary endpoint was the change from baseline in the average number of migraine days per month over the 3-month double-blind period. Key secondary endpoints included changes in the number of days per month with headache of at least moderate severity and the proportion of patients achieving a reduction of 50% or more in monthly migraine days.

Efficacy outcomes

Among the 234 participants included in the full analysis population, fremanezumab was associated with a greater reduction in migraine frequency than placebo. The least-squares mean reduction in monthly migraine days was 2.5 days with fremanezumab compared with 1.4 days with placebo, corresponding to a between-group difference of 1.1 days (P = .02). Reductions in days per month with headache of at least moderate severity were also greater with fremanezumab than placebo (2.6 vs 1.5 days; difference, 1.1 days; P = .02).

Nearly half of patients treated with fremanezumab achieved a clinically meaningful response. A reduction of at least 50% in monthly migraine days occurred in 47.2% of participants receiving fremanezumab compared with 27.0% of those receiving placebo (P = .002). Fremanezumab was also associated with a greater reduction in the number of days per month in which acute headache medication was used.

Andrew D. Hershey, MD, PhD, the study’s lead author and endowed chair and director of neurology at Cincinnati Children’s Hospital Medical Center, emphasized the clinical relevance of these findings. “Helping to prevent migraine attacks in children and adolescents is critical to supporting their healthy development and education, including missed school days, disability and overall social well-being,” he said. “The SPACE trial demonstrates that a CGRP-targeted preventive therapy like fremanezumab-vfrm (AJOVY) can significantly reduce the frequency of attacks of migraine in youth, giving physicians critical evidence to guide care for this underserved population.”

Safety and tolerability

The safety profile of fremanezumab in the pediatric population was consistent with that observed in adult studies. Adverse events were generally mild to moderate in severity, and no new safety signals were identified. The most common adverse event was injection-site erythema, reported in 9.8% of patients receiving fremanezumab and 5.4% of those receiving placebo. Serious adverse events were uncommon, and no deaths occurred during the trial.

Investigators reported no clinically meaningful differences between treatment groups in laboratory measures, vital signs, electrocardiographic findings, or assessments of suicidal ideation and behavior. Overall, the findings suggest that fremanezumab was well tolerated over the 3-month treatment period.

Clinical implications

Migraine is a common neurologic condition in children and adolescents and is associated with missed school days, impaired academic performance, and reduced quality of life. Preventive treatment options for this population have historically been limited, and many commonly used therapies are associated with tolerability concerns.

The SPACE trial provides randomized, controlled evidence supporting the efficacy and safety of CGRP-targeted therapy in pediatric episodic migraine. According to the investigators, longer-term follow-up is ongoing to further evaluate the durability of response and long-term safety in this population.

References

1. Teva. AJOVY® (fremanezumab-vfrm) Significantly Reduced Monthly Migraine and Headache Days in Children and Adolescents with Episodic Migraine Compared to Placebo in the SPACE Trial; Results Published in New England Journal of Medicine. Teva. January 14, 2026. Accessed January 15, 2026. https://www.tevapharm.com/news-and-media/latest-news/ajovy-fremanezumab-vfrm-significantly-reduced-monthly-migraine-and-headache-days-in-children-and-adole/
2. Hershey AD, Szperka CL, Barbanti P, et al. Fremanezumab in Children and Adolescents with Episodic Migraine. New England Journal of Medicine. 2026;394(3):243-252. doi:https://doi.org/10.1056/nejmoa2504546
3. Fitch J. FDA approves fremanezumab-vfrm for migraine prevention in children aged 6 years, older. Contemporary Pediatrics. August 5, 2025. Accessed January 15, 2026. https://www.contemporarypediatrics.com/view/fda-approves-fremanezumab-vfrm-for-migraine-prevention-in-children-aged-6-years-older