Fremanezumab demonstrates efficacy and safety in pediatric patients with episodic migraine: Results from the phase 3 SPACE study

1 May 2025

STUDY DESIGN

Approximately three-quarters of children and adolescents with migraine will continue to experience migraine into adulthood, contributing to a significant long-term disease burden in this population.¹ The phase 3 SPACE trial was designed to evaluate the efficacy and safety, of fremanezumab, a monoclonal antibody targeting the calcitonin gene-related peptide (CGRP) pathway, for the preventive treatment of episodic migraine (EM) in pediatric patients aged 6 to 17 years.¹

This multicenter, randomized, double-blind, placebo-controlled, parallel-group study enrolled 237 participants, who were randomized 1:1 to receive weight-based monthly subcutaneous injections of fremanezumab (120mg for participants <45kg; 225mg for ≥45kg) or matching placebo over a 12-week double-blind treatment period.¹ Eligible participants had a documented diagnosis of migraine for at least six months and reported no more than 14 headache days per month at baseline.¹ A total of 234 participants were included in the efficacy analysis (fremanezumab, n=123; placebo, n=111).¹ Baseline characteristics were well balanced across both groups, with a mean age of 13.3 years in the fremanezumab group.¹

The primary endpoint was the least-squares (LS) mean change from baseline in average monthly migraine days (MMD) during the 12-week treatment phase.¹ Secondary endpoints included the LS mean change from baseline in monthly headache days of at least moderate severity (MHD) and the proportion of participants achieving a ≥50% reduction in MMD over 3 months.¹ Additional secondary endpoints included the LS mean change from baseline in the average number of monthly days with acute migraine medication use over 3 months, as well as assessments using the Pediatric Migraine Disability Assessment (PedMIDAS) and the Pediatric Quality of Life Inventory (PedsQL).¹ Predefined subgroup analyses were conducted by age group (6-11 years vs. 12-17 years) and sex.¹

FINDINGS

Primary endpoint:

The primary endpoint was LS mean change from baseline in average MMD during the 12-week treatment phase¹
Fremanezumab significantly reduced MMD compared to placebo, with separation observed as early as month 1 (LS mean change from baseline: -2.5 (95% CI: -3.22 to -1.72) vs. -1.4 (95% CI: -2.22 to -0.67); p=0.0210)¹

Secondary endpoints:

Secondary endpoints included the LS mean change from baseline in MHD of at least moderate severity, the proportion of participants achieving a ≥50% reduction in MMD over 3 months, the LS mean change from baseline in the average number of monthly days with acute migraine medication use over 3 months, as well as PedMIDAS and PedsQL assessments¹
A greater reduction in MHD was observed in the fremanezumab group compared to placebo, evident from month 1 (LS mean change: -2.6 (95% CI: -3.42 to -1.83) vs. -1.5 (95% CI: -2.32 to -0.66); p=0.0172)¹
There is a significantly higher proportion of participants in the fremanezumab group achieved ≥50% reduction in MMD compared to placebo over 3 months (47.2% vs. 27.0%; p=0.0016)¹
Fremanezumab significantly reduced the use of acute migraine medications compared to placebo, beginning at month 1 (LS mean change from baseline: -2.1 (95% CI: -2.64 to -1.48) vs. -1.0 (95% CI: -1.56 to -0.36); p=0.0016)¹
Fremanezumab demonstrated a non-significant trend toward improvement in migraine-related disability, as measured by the PedMIDAS total score; however, no corresponding trend was observed in overall quality of life by the PedsQL total score¹
Subgroup analyses showed that fremanezumab resulted in a greater reduction in MMD compared to placebo in the age groups: -3.4 vs. -1.7 in participants aged 6-11 years, and -2.7 vs. -1.8 in those aged 12-17 years¹
When analyzed by sex, male participants receiving fremanezumab experienced a reduction of -3.5 MMD versus -2.2 with placebo, while female participants had a reduction of -2.3 compared to -1.5 with placebo, respectively¹

Safety:

The proportion of patients reporting at least one adverse event (AE) was similar between the fremanezumab vs. placebo groups (55% vs. 49%)¹
No AEs leading to death were reported in either group¹

References

Hershey AD, et al. Efficacy and safety of fremanezumab for the preventive treatment of episodic migraine in children and adolescents: A phase 3, randomized, double-blind, placebo-controlled study. Presented at the American Academy of Neurology (AAN) Annual Meeting 2025; April 5-9, 2025.