Research Summary

Fremanezumab Reduces Migraine Days in Children, Adolescents with Episodic Migraine

Edited by:
Anthony Calabro, MA

Key Highlights

  • Fremanezumab significantly reduced monthly migraine days compared with placebo over 3 months.
  • Nearly half of treated participants achieved a ≥50% reduction in migraine days.
  • Injection-site erythema was the most common adverse event; no new safety signals were identified.

Fremanezumab, a monoclonal antibody targeting calcitonin gene–related peptide (CGRP), significantly reduced migraine frequency in children and adolescents with episodic migraine, according to a phase 3, randomized, placebo-controlled trial published in The New England Journal of Medicine. The findings provide prospective evidence supporting the use of CGRP-targeted preventive therapy in pediatric populations.

The multicenter trial enrolled participants aged 6 to 17 years with episodic migraine, defined as a history of migraine for at least 6 months and no more than 14 headache days per month. Participants were randomly assigned to receive monthly subcutaneous fremanezumab or placebo for 3 months, with dosing based on body weight.

The study was conducted at 89 sites across 9 countries between August 2020 and March 2024. Eligible participants were randomized in a 1:1 ratio to fremanezumab (120 mg for those weighing <45 kg or 225 mg for those ≥45 kg) or a matched placebo. The primary endpoint was the change from baseline in the average monthly number of migraine days during the double-blind period. Key secondary endpoints included changes in the number of headache days of at least moderate severity and the proportion of participants achieving a ≥50% reduction in migraine days.

Study Findings
Among 234 participants in the full analysis population, fremanezumab was associated with a greater reduction in migraine days per month than placebo. The least-squares mean reduction was 2.5 days with fremanezumab versus 1.4 days with placebo, yielding a between-group difference of 1.1 days (P = .02). A similar difference was observed for days with headache of at least moderate severity, with reductions of 2.6 days and 1.5 days, respectively (P = .02).

A significantly higher proportion of participants receiving fremanezumab achieved a ≥50% reduction in monthly migraine days compared with placebo (47.2% vs 27.0%; P = .002). Use of acute headache medication also decreased more with fremanezumab than with placebo. Injection-site erythema was the most frequently reported adverse event, occurring in 9.8% of the fremanezumab group and 5.4% of the placebo group.

Clinical Implications
According to the study authors, the findings suggest that fremanezumab provides clinically meaningful reductions in migraine frequency and headache burden in children and adolescents with episodic migraine. The safety profile observed in this population was similar to that reported in adult trials, with most adverse events being mild to moderate in severity.

Expert Commentary
“Treatment with fremanezumab for 3 months led to significant reductions in the number of migraine days per month, days per month with headache of at least moderate severity, and days per month in which acute headache medication was used, as compared with placebo, in children and adolescents with episodic migraine,” the researchers concluded.

Reference
Hershey AD, Szperka CL, Barbanti P, et al. Fremanezumab in children and adolescents with episodic migraine. N Engl J Med. 2026;394:243-252. doi:10.1056/NEJMoa2504546