Abstract
Background: Fremanezumab, a humanized monoclonal antibody that selectively targets calcitonin gene-related peptide, is approved for the prevention of migraine in adults. Evidence from randomized, controlled trials in children and adolescents is needed.
Methods: We randomly assigned participants 6 to 17 years of age with a diagnosis of episodic migraine (defined as migraine for ≥6 months and a history of ≤14 headache days per month) to receive monthly subcutaneous injections of fremanezumab (120 mg for participants with a body weight of <45 kg and 225 mg for those with a body weight of ≥45 kg) or matched placebo for 3 months. Participants were allowed to use migraine-specific medications to treat acute headaches. The primary end point was the change from baseline in the average number of migraine days per month. Key secondary end points included the change in the number of days per month with headache of at least moderate severity and a reduction of 50% or more in the number of migraine days per month.
Results: Of 237 participants who underwent randomization, 234 were included in the full analysis population: 123 in the fremanezumab group (36 received the 120-mg dose and 87 received the 225-mg dose) and 111 in the placebo group. Fremanezumab reduced the number of migraine days per month by 2.5 as compared with 1.4 with placebo (difference, 1.1; P = 0.02) and the number of days per month with headache of at least moderate severity by 2.6 as compared with 1.5 with placebo (difference, 1.1; P = 0.02). The percentage of participants who had a reduction of 50% or more in the number of migraine days per month was 47.2% with fremanezumab and 27.0% with placebo (P = 0.002). Injection-site erythema was the most common adverse event with fremanezumab (9.8% of participants, vs. 5.4% with placebo).
Conclusions: Among children and adolescents with episodic migraine, fremanezumab resulted in greater reductions in the number of migraine days and headache days than placebo. Injection-site erythema was the most common adverse event with fremanezumab. Longer follow-up is required to further understand the efficacy and safety of the drug in this population. (Funded by Teva Pharmaceuticals; ClinicalTrials.gov number, NCT04458857.).
Iannone LF, Romozzi M, Papetti L, Toldo I, Valeriani M, Geppetti P. Pharmacokinetics and Pharmacodynamics, Efficacy and Safety of Fremanezumab in Children and Adolescents with Migraine. Eur J Drug Metab Pharmacokinet. 2026 Mar;51(2):133-139. doi: 10.1007/s13318-026-00990-7. Epub 2026 Mar 13. PMID: 41824241; PMCID: PMC13031235.
Abstract
Migraine affects up to 11% of children and adolescents, leading to substantial disability through school absenteeism, cognitive impairment, and reduced quality of life. Traditionally, preventive treatment options for this population have been limited to the off-label use of nutraceuticals, antiseizure medications, calcium channel blockers, serotonin modulators, antidepressants, or beta-blockers, with limited efficacy and tolerability data. Monoclonal antibodies targeting the calcitonin gene-related peptide (CGRP) pathway have transformed adult migraine prevention, and fremanezumab is the first in this class to receive regulatory approval for pediatric use. In August 2025, the US Food and Drug Administration approved fremanezumab for the preventive treatment of episodic migraine in patients aged 6-17 years weighing at least 45 kg, based on the pivotal phase three SPACE trial. This randomized, placebo-controlled study demonstrated significant reductions in monthly migraine and headache days, with nearly half of treated participants achieving a ≥50% response rate, and a safety profile consistent with adult data. In this review, we provide an integrated, pediatric-focused synthesis of the pharmacokinetic, pharmacodynamic, and regulatory evidence supporting fremanezumab use in children and adolescents. In particular, we contextualize population pharmacokinetic modeling and pediatric phase 1 data to explain the rationale for weight-based dosing, exposure matching with adults, and the selection of the dosing regimens used in clinical trials and regulatory labeling. Pharmacokinetic analyses indicate that fremanezumab follows a two-compartment model with first-order absorption and a terminal half-life of approximately 30 days in pediatric patients, similar to adults, with body weight as the primary determinant of exposure. Finally, we discuss unresolved issues related to long-term CGRP blockade during growth, including theoretical effects on vascular regulation, bone metabolism, and neurodevelopment. Overall, fremanezumab represents a novel, mechanism-based preventive option for older children and adolescents with episodic migraine, while highlighting the need for continued longitudinal studies to define its long-term safety and optimal role in pediatric migraine management.
Friedman DI, Cohen JM. Fremanezumab: a disease-specific option for the preventive treatment of migraine, including difficult-to-treat migraine. Emerg Top Life Sci. 2020 Sep 8;4(2):179-190. doi: 10.1042/ETLS20200018. PMID: 32832978; PMCID: PMC7487173.
Abstract
Fremanezumab is a fully humanized monoclonal antibody (IgG2Δa) that targets calcitonin gene-related peptide (CGRP), a key neuropeptide involved in the pathophysiology of migraine. Fremanezumab is approved for quarterly and monthly subcutaneous dosing for the preventive treatment of migraine in adults. The phase 3 clinical development program for fremanezumab aimed to evaluate the efficacy of this preventive treatment across different patient populations, including those with difficult-to-treat migraine. Two pivotal 12-week, phase 3, placebo-controlled studies investigated quarterly and monthly dosing of fremanezumab in participants with chronic migraine (HALO CM) and episodic migraine (HALO EM). The efficacy of fremanezumab was further explored in individuals with difficult-to-treat chronic or episodic migraine in the 12-week FOCUS study, which enrolled participants who had previously experienced an inadequate response to 2-4 pharmacological classes of migraine preventive medications. The long-term efficacy of fremanezumab was assessed in a 12-month long-term study (HALO LTS), which enrolled participants completing the 12-week HALO studies and new participants. Across these studies, treatment with fremanezumab dosed quarterly or monthly provided significant reductions in the frequency of migraine days, headache days of at least moderate severity, and migraine- and headache-related disability compared with placebo. Sustained improvements were seen with long-term fremanezumab treatment. Subgroup analyses of participants with difficult-to-treat migraine (those with comorbid depression, overuse of acute headache medications, and concomitant use of other migraine preventive medications) demonstrated the effectiveness of quarterly or monthly fremanezumab in these populations. Ongoing studies are further exploring the potential benefits of fremanezumab in difficult-to-treat migraine and other headache and pain disorders.
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