Published SPACE Study Reinforces Efficacy of Fremanezumab for Pediatric Episodic Migraine

A randomized, double-blind, placebo-controlled phase 3 trial (NCT044588857) evaluating monthly administration of fremanezumab (Ajovy; Teva) for the preventive treatment of episodic migraine in children and adolescents aged 6–17 years showed statistically significant reductions in migraine burden compared with placebo.¹ Published in the New England Journal of Medicine, the now complete findings supported the FDA’s August 2025 decision to expand the indication of fremanezumab to pediatric patients, addressing a longstanding gap in evidence-based migraine prevention for this population.²

SPACE Study Overview

Coined SPACE, the trial, enrolled 237 children and adolescents 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 234 participants were included in the full analysis population and participants were randomly assigned to receive monthly subcutaneous fremanezumab or matched placebo for 12 weeks. Dosing was weight based, with 120 mg administered to participants weighing less than 45 kg and 225 mg to those weighing 45 kg or more.

Led by Andrew Hersey, MD, PhD, FAAN, FAHS, endowed chair and director of the Division of Neurology at Cincinnati Children’s in Ohio, investigators designated the primary endpoint as the change from baseline in average monthly migraine days. Moreover, key secondary endpoints included changes in monthly days with at least moderate headache severity and the proportion of patients achieving a 50% or greater reduction in migraine days.¹

All told, fremanezumab was associated with greater reductions in migraine burden compared with placebo. Overall, mean monthly migraine days decreased by 2.5 days in the fremanezumab group versus 1.4 days with placebo (between-group difference, 1.1 days; P = .02). Reductions in monthly moderate-to-severe headache days also favored fremanezumab (–2.6 vs –1.5 days; P = .02), and a higher proportion of treated patients achieved at least a 50% reduction in migraine days (47.2% vs 27.0%; P = .002).¹

Safety and Tolerability

Study authors noted that the safety profile was consistent with that observed in adults. The most commonly reported adverse event was injection-site erythema (9.8% with fremanezumab vs 5.4% with placebo). Rates of overall adverse events (AEs) and serious AEs were generally similar between groups, with no new safety signals identified during the 3-month period.¹

Interpretation and Limitations

The SPACE trial demonstrated statistically significant reductions in migraine and headache days with fremanezumab versus placebo over 12 weeks in a pediatric episodic migraine population, reinforcing the biological rationale for CGRP pathway antagonism across age groups. However, follow-up beyond three months is limited, and long-term safety, impact on functional outcomes (eg, school performance), and comparisons with conventional preventive therapies require further study. Additionally, the approved pediatric indication applies only to patients weighing more than 45 kg due to formulation constraints.⁶

Future investigations should focus on longer-term outcomes, real-world effectiveness, and comparative effectiveness against established preventive agents and nonpharmacologic interventions. Assessing efficacy and safety in younger children (<6 years) and in those less than 45 kg remains an unmet need.

Regulatory Context and Pediatric Approval

Fremanezumab, a fully humanized monoclonal antibody targeting calcitonin gene-related peptide (CGRP)—a key mediator in migraine pathophysiology, was initially approved in 2018 for preventive migraine treatment in adults. Supported by the SPACE trial data, the FDA expanded the indication in August 2025 to include episodic migraine prevention in children and adolescents aged 6–17 years who weigh at least 45 kg.^2,6 The pediatric label specifies a 225 mg monthly subcutaneous regimen for eligible patients, with administration by a trained caregiver or healthcare provider.¹⁰

Clinical Context: Pediatric Migraine Management

Migraine affects an estimated 7.7% of children and adolescents in population studies, with prevalence increasing in older age groups.^2,3 Pediatric migraine is associated with significant disability, yet evidence guiding preventive therapy is less robust than in adults. Traditional preventive agents used off-label in children include topiramate, propranolol, and amitriptyline, with mixed efficacy and tolerability profiles. Behavioral and lifestyle strategies such as cognitive behavioral therapy also play a role in comprehensive management. ^4,5

Professional guidelines have emphasized individualized risk–benefit assessment when considering preventive therapy, particularly given the placebo response observed in pediatric studies. Prior to the SPACE data, no anti-CGRP monoclonal antibody had high-quality pediatric evidence, and preventive options were limited.

REFERENCES
1. Hershey A, Szperka C, Barbanti P, et al. Fremanezumab in Children and Adolescents with Episodic Migraine. N Engl J Med. 2026;394(3):243-252. doi:10.1056/NEJMoa2504546
2. FDA Approves Expanded Indication for AJOVY® (fremanezumab-vfrm), The First Anti-CGRP Preventive Treatment for Pediatric Episodic Migraine. Teva Pharmaceuticals. News Release. August 6, 2025. Accessed January 10, 2026 https://www.tevapharm.com/news-and-media/latest-news/fda-approves-expanded-indication-for-ajovy-fremanezumab-vfrm-the-first-anti-cgrp-preventive-treatment/
3. Al Khalili Y, Asuncion RMD, Chopra P. Migraine Headache in Childhood. In: StatPearls. Treasure Island (FL): StatPearls Publishing; 2025. https://www.ncbi.nlm.nih.gov/books/NBK557813/
4. Treatment of Migraine in Children. American Migraine Foundation. September 14, 2017. Accessed February 10, 2026. https://americanmigrainefoundation.org/resource-library/treating-migraine-in-children/
5. Gazerani P, et al. Episodic Migraine in the Pediatric Population: Behavioral and Nonpharmacological Approaches. PMC article. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11876209/
6. AJOVY® (fremanezumab-vfrm) Prescribing Information, FDA Label (2025). https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/761089s031lbl.pdf