The U.S. Food and Drug Administration approved fremanezumab (Ajovy; Teva) on August 6, 2025, for the preventive treatment of episodic migraine in children and adolescents aged 6-17 years weighing at least 45 kg. This milestone marks the first anti-calcitonin gene-related peptide (CGRP) monoclonal antibody approved for use in the pediatric population, addressing a longstanding gap in migraine care for younger patients.
Addressing Critical Unmet Need
Migraine affects approximately 7.7% of children and adolescents, representing a highly prevalent and disabling neurological condition in this population. For those living with episodic migraine, defined as fewer than 15 headache days per month, the burden can be substantial, disrupting academic performance and social engagement.
"For many years, we had no proven treatments for children and teenagers with migraine. Now, with fremanezumab, we finally have a safe and effective option that can truly make a difference," said Patricia Pozo-Rosich, MD, PhD, study investigator of the pivotal SPACE trial and head of the neurology department at the Vall d'Hebron University Hospital.
Preventive treatment options for pediatric migraine have historically been limited, with most therapies used off-label and lacking robust pediatric-specific data. Although topiramate is FDA-approved for adolescent migraine, its efficacy has been inconsistent in trials. Previous studies, such as the CHAMP trial, fueled the long-standing perception that placebo effects were too strong to overcome in pediatric populations, leaving clinicians with limited strategies beyond lifestyle interventions or off-label attempts.
Mechanism and Administration
Fremanezumab is a fully humanized monoclonal antibody that targets CGRP, a neuropeptide involved in the transmission of migraine pain and vasodilation during migraine attacks. By binding to CGRP and preventing its interaction with receptors, fremanezumab interrupts a key pathway in migraine development. The drug is administered as a monthly 225 mg subcutaneous injection by a healthcare professional or at home by the patient or caregiver.
Pivotal SPACE Trial Results
The FDA approval was supported by results from the Phase III SPACE trial (NCT04458857), a randomized, double-blind, placebo-controlled study enrolling 237 children and adolescents aged 6-17 years, each weighing at least 45 kg and experiencing episodic migraine. Participants were randomized to receive either fremanezumab or placebo over a 12-week treatment period.
Among the 234 efficacy-evaluable participants, the study demonstrated statistically significant improvements across multiple endpoints:
- Monthly migraine days reduction: -2.5 days with fremanezumab versus -1.4 days with placebo (p = 0.0210)
- Monthly headache days reduction: -2.6 versus -1.5 (p = 0.0172)
- ≥50% responder rate: 47.2% in the treatment group versus 27.0% with placebo (p = 0.0016)
The efficacy remained consistent across subgroups by age (6-11 and 12-17 years) and sex, demonstrating broad applicability across the pediatric population studied.
Safety Profile
Adverse events occurred in 55% of patients receiving fremanezumab, compared with 49% in the placebo group. Most adverse events were mild to moderate in severity. Serious adverse events were rare (≤3%), and discontinuation due to adverse events occurred in less than 1% of participants. Importantly, the safety profile in this younger cohort was consistent with that observed in adult populations, and no new safety signals emerged.
Clinical Impact
The approval of fremanezumab represents a significant step forward for a population historically underserved by approved preventive therapies. Unlike many oral therapies used off-label in pediatric settings, fremanezumab has a well-characterized mechanism, consistent monthly dosing, and a proven safety and efficacy profile from a large, controlled trial in the target population.
This development is particularly meaningful given the limited number of FDA-approved preventive treatments for pediatric migraine, which often leads to delays in adequate care and reliance on less targeted interventions. With fremanezumab now available for pediatric use, clinicians may be better equipped to tailor preventive strategies based on a patient's age, weight, and clinical profile, potentially improving both adherence and long-term outcomes.
Fremanezumab was first approved in 2018 as a preventive treatment of migraine in adults, becoming the second marketed CGRP therapy behind erenumab (Aimovig; Amgen). The drug comes with monthly and quarterly dosing options for adults and is administered as a 225 mg/1.5 mL single dose injection in a pre-filled autoinjector or pre-filled syringe.
