Fremanezumab Reduces Migraine Days in Pediatric Episodic Migraine
Key Clinical Summary
- Fremanezumab significantly reduced monthly migraine days compared with placebo in children and adolescents aged 6 to 17 years.
- Nearly half of treated participants achieved a ≥50% reduction in migraine days over 3 months.
- Injection-site erythema was the most common adverse event, with no new safety signals identified.
Fremanezumab, a monoclonal antibody targeting calcitonin gene–related peptide (CGRP), is approved for migraine prevention in adults, but pediatric evidence has been limited. In a recent randomized, placebo-controlled trial published in The New England Journal of Medicine, researchers found that fremanezumab significantly reduced monthly migraine days compared with placebo in children and adolescents with episodic migraine.
Study Design
The phase 3 trial enrolled children and adolescents 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. A total of 237 participants were randomized, with 234 included in the full analysis population.
Participants received monthly subcutaneous injections of fremanezumab or placebo for 3 months. Dosing was weight-based: those weighing less than 45 kg received 120 mg and those weighing 45 kg or more received 225 mg. The use of migraine-specific medications to treat acute headaches was permitted throughout the study. Researchers evaluated the change from baseline in the average number of migraine days per month as the primary outcome.
Key Findings
Fremanezumab reduced monthly migraine days by 2.5 days, compared with a reduction of 1.4 days in the placebo group, yielding a between-group difference of 1.1 days (P = 0.02).
Key secondary endpoints also favored fremanezumab. Days per month with headache of at least moderate severity decreased by 2.6 days with fremanezumab versus 1.5 days with placebo (difference, 1.1 days; P = 0.02). A reduction of 50% or more in monthly migraine days was achieved by 47.2% of patients receiving fremanezumab, compared with 27.0% in the placebo group (P = 0.002).
Regarding safety, injection-site erythema was the most frequently reported adverse event, occurring in 9.8% of fremanezumab-treated participants versus 5.4% in the placebo group. Most adverse events were nonserious and no safety signals were observed.
Clinical Implications
Migraine attacks may pose significant burden on children and adolescents, impacting school performance, social engagement, and overall quality of life. Still, preventive treatment options in this population remain limited.
These findings suggest that CGRP-targeted therapy with fremanezumab may offer a clinically meaningful reduction in migraine burden for pediatric patients with episodic migraine. The magnitude of benefit is consistent with adult trials, supporting the biologic relevance of CGRP in pediatric migraine pathophysiology.
Expert Commentary
“The population studied in this trial was reflective of the real-world clinical population of children and adolescents with episodic migraine, and the inclusion of participants across age ranges and geographic regions enhances the generalizability of these results,” noted Andrew D. Hershey, MD, PhD, Cincinnati Children’s Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, and study coauthors.
The authors also emphasized the need for longer-term studies to confirm efficacy and safety findings, and to inform clinical use and guideline development in pediatric migraine prevention.
