The multicenter, double-blind, parallel-group, phase 3 study—led by headache medicine specialist and child neurologist Andrew Hersey, MD, PhD, FAAN, endowed chair and director of the division of neurology at Cincinnati Children's Hospital Medical Center—randomized participants aged 6–17 years, with a migraine diagnosis for ≥6 months and history of ≤14 headache days/month, 1:1 to monthly fremanezumab (<45kg, 120 mg; ≥45kg, 225 mg) or placebo for 12 weeks.
“The primary endpoint was a mean change from baseline in average monthly migraine days (MMD), with secondary endpoints including mean change from baseline in monthly headache days of at least moderate severity (MHD) and proportion of participants achieving a ≥50% reduction in MMD," the investigators wrote in their abstract.
Over three months, fremanezumab significantly reduced MMD vs. placebo (-2.5 vs -1.4, p=0.0210). The reduction in MHD was significantly greater with fremanezumab versus placebo (–2.6 vs –1.5; p=0.0172), as was the 50 percent response rate (47.2 percent vs 27percent (p=0.0016).
The trial also included subgroup analyses conducted by age (6–11 and 12–17 years) and sex. In all subgroups, mean changes from baseline in MMD favored fremanezumab over placebo: age (6–11 years: – 3.4 vs –1.7; 12–17 years: –2.7 vs –1.8) and sex (male: –3.5 vs –2.2; female: –2.3 vs –1.5).
The proportion of participants reporting more than one adverse event was similar across treatment groups and the proportion of participants with serious adverse events (less than 3 percent) and adverse events leading to discontinuation were low at less than 1.0 percent.
“These findings demonstrate the efficacy, safety, and tolerability of fremanezumab in children and adolescents with episodic migraine," the investigators concluded.
“This is extremely significant," said Jessica Ailani, MD, clinical professor of neurology at MedStar Georgetown University Hospital and director of the MedStar Georgetown Headache Center in Washington, DC. “This is the first readout of study results for any of the anti-CGRP treatments for migraine prevention in the pediatric population, and as a field we've been holding our breath hoping for an effective treatment. This data is positive, and I'm extremely encouraged."
“While we have real-world evidence showing that these anti-CGRP treatments, especially the monoclonal antibodies, are effective in the pediatric population, that real-world data has been focused more on patients who are refractory to other treatments," Dr. Ailani said. “So it is useful to have trial data in groups of patients who aren't necessarily refractory, and in an age range that includes fairly young patients."
She also praised the trial's breakdown by sex. “There has been some controversy about whether anti-CGRP preventive treatments are equally effective in women and men," she said. “They broke that down, and it looked like maybe it was about a quarter of a day more effective in the male population than the female, but overall, it looked to be very effective in both sexes."
Dr. Ailani noted that in the pediatric population, especially with injectables, there are often a lot of dropouts because of adverse events, so the low dropout rate was impressive. “But I'd like to see if the actual adverse event profile resembled the adult studies, where we didn't really see much other than injection site reactions."
A headache therapy outperforming placebo in the pediatric population is a significant achievement, Dr. Ailani said. “In migraine, we have really struggled to show efficacy compared to placebo, even for acute treatments that we know work really well," she said.
“If we get these patients on track early with migraine-specific treatments, is it possible that they can grow up and not develop chronic migraine?" she asked. “I would love to see long-term data on these types of treatments, and what the headache freedom response rates look like over the course of a year for patients who remain on treatment. Could we see rates of chronic migraine go down over time? That's a really exciting possibility."
Disclosures: Dr. Hershey has nothing to disclose. Dr. Ailani received consulting fees from Abbvie, Eli Lilly, Lundbeck, Satsuma, Pfizer, Gore, Ipsen, Merz, Scilex Dr. Reddy, Linpharma, Vectura, and Aeon. Dr. Ailani serves on a scientific advisory or data safety monitoring board for Abbvie, Linpharma, and Aeon. Dr. Ailani's institution has received research support from Ipsen, Parema, and Lundbeck.
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
Andrew D. Hershey1, Christina L. Szperka2, Piero Barbanti3, Patricia Pozo-Rosich4, Petra Bittigau5, Steve Barash6, Sally Garnett6, Juline Bryson6, Yoel Kessler7, Yael Carmeli Schwartz7, Xiaoping Ning6
1Cincinnati Children’s Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH, USA, 2Children’s Hospital of Philadelphia and Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA, 3Headache and Pain Unit, IRCCS San Raffaele, Rome, Italy, and San Raffaele University, Rome, Italy, 4Headache Unit and Research Group, Vall d’Hebron Hospital and Research Institute, Universitat Autonoma de Barcelona, Barcelona, Spain, 5Charité-Universitätsmedizin Berlin, Berlin, Germany, 6Teva Branded Pharmaceutical Products R&D, Inc., West Chester, PA, USA, 7Teva Pharmaceutical Industries Ltd., Tel Aviv, Israel
Objective:
The SPACE study (NCT04458857) evaluated the efficacy, safety, and tolerability of fremanezumab in children and adolescents with episodic migraine (EM).
Background:
Fremanezumab is a calcitonin gene-related peptide pathway monoclonal antibody approved for preventive migraine treatment in adults.
Design/Methods:
In this multicenter, double-blind, parallel-group, Phase 3 study, participants aged 6–17 years, with a migraine diagnosis for ≥6 months and history of ≤14 headache days/month, were randomized (1:1) to monthly fremanezumab (<45kg, 120 mg; ≥45kg, 225 mg) or placebo for 12 weeks. Primary endpoint: least-squares (LS) mean change from baseline in average monthly migraine days (MMD) during the double-blind period. Secondary endpoints included LS mean change from baseline in monthly headache days of at least moderate severity (MHD) and proportion of participants achieving a ≥50% reduction in MMD. Subgroup analyses were conducted by age (6–11 and 12–17 years) and sex.
Results:
Of 237 randomized participants, 234 (6–11 years, n=63; 12–17 years, n=171; male, n=105; female, n=129) were included in the efficacy analysis (fremanezumab, n=123; placebo, n=111). Fremanezumab significantly reduced MMD versus placebo (–2.5 vs –1.4; p=0.0210) over 3 months. LS mean changes from baseline in MMD favored fremanezumab over placebo in subgroups stratified by age (6–11 years: –3.4 vs –1.7; 12–17 years: –2.7 vs –1.8) and sex (male: –3.5 vs –2.2; female: –2.3 vs –1.5). The reduction in MHD was significantly greater with fremanezumab versus placebo (–2.6 vs –1.5; p=0.0172), as was the 50% response rate (47.2% vs 27.0%; p=0.0016). The proportion of participants reporting ≥1 adverse event (AE) was similar across treatment groups (fremanezumab, 55%; placebo, 49%). The proportion of participants with serious AEs (≤3%) and AEs leading to discontinuation (<1%) were low.
Conclusions:
These findings demonstrate the efficacy, safety, and tolerability of fremanezumab in children and adolescents with EM.
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