An Anti-CGRP Antibody Expands the Pediatric Migraine Toolbox: A Look at the Data

A recent randomized controlled trial testing fremanezumab in children and adolescents with episodic migraine showed a reduction in monthly migraine days.

Migraine is very common in children and adolescents, with one recent systematic review and meta-analysis estimating the prevalence of the condition at 11% in this population. New treatments for kids with migraine are needed, but randomized trial data for anti-CGRP monoclonal antibodies, one of the field’s most important recent therapies for adults, has been lacking for youngsters.

But now, the results of a new prospective, randomized controlled trial testing fremanezumab, an anti-CGRP antibody, in kids with episodic migraine have been published in the New England Journal of Medicine. The new publication gives the field the opportunity to look at the data that led to regulatory approval of the antibody for episodic migraine prevention in children and adolescents.

The trial, which included 237 participants between the ages of six and 17 years with episodic migraine, reported a greater reduction from baseline in monthly migraine days, the study’s primary outcome, compared to placebo, with similarly encouraging results on a number of secondary outcomes. The drug also appeared safe.

Serena Orr, a pediatric headache specialist and researcher at the University of Calgary and Alberta Children’s Hospital, Canada, told Migraine Science Collaborative that the results represent “an exciting development.”

“The data from this study suggest that this is a safe and effective drug, with limited side effects, which is great,” she said. “It’s very exciting that we have completed a CGRP trial for kids now, and that it gives us something ‘on label’ we can use as an option for treatment,” according to Orr, who was not involved with the new work.

The trial results appeared in the January 15, 2026, issue of NEJM.

Challenges inherent to pediatric trials
Researchers attempting to carry out drug trials in younger patients face a host of obstacles. First, there are ethical concerns surrounding risk-benefit balance. Next, there’s the matter of informed consent; physicians must gain assent not only from the kids to participate, but their parents, too, which can be a tall order. Then there are substantial physiological differences among kids of different ages, which adds heterogeneity to the trials. Clinical trials for younger populations are often quite hard to fund, too.

One of the biggest challenges of pediatric clinical trials, however, is the placebo effect, according to Andrew Hershey, Cincinnati Children’s Hospital Medical Center and University of Cincinnati College of Medicine, US, and first author of the new fremanezumab trial.

“Most pharmaceutical trials are generally done in adults first, and the results are released before we do trials in children and adolescent populations,” he explained. “That means there is a heightened expectation and placebo response. When you compare children and adolescent and adult studies, ultimately the efficacy of the drug or device is generally about the same. But when you factor in that increased placebo response, it’s hard to see a separation of the intervention from placebo in the results, which makes it harder to get the kind of positive results that will lead to drug approval.”

With anti-CGRP monoclonal antibody trials proving the efficacy and safety of these drugs for migraine prevention in adults, it was natural to ask whether they would also work in children and adolescents with migraine, and whether a trial could clear the hurdle of an enhanced placebo response.

So Hershey and colleagues recruited 237 pediatric participants from 89 different sites in nine countries. Seventy-four of those sites enrolled at least one participant between the ages of six and 17 years who had been previously diagnosed with episodic migraine (defined as migraine for at least six months, with 14 or fewer monthly headache days).

Each trial participant needed to have at least four monthly headache days in each of the three months before screening. After a one-month baseline period, participants were then randomly assigned to receive a monthly injection of fremanezumab (123 participants), or a placebo injection (111 participants), for three months.

Based on the results from anti-CGRP monoclonal antibody trials in adults, Hershey said that he hoped the trial would meet its primary endpoint of a significant reduction from baseline in the average number of migraine days per month. Once he and his team analyzed the data from the 234 participants who were included in the full analysis population, they found that fremanezumab did exactly that: It reduced the average number of migraine days per month by 2.5 days, compared to 1.4 days with placebo, a difference of 1.1 days.

The trial also reached some key secondary endpoints. First, fremanezumab reduced the average number of days per month with headache of at least moderate severity by 2.6 days, compared to 1.5 days with placebo. Second, 47.2% of participants in the fremanezumab group saw a reduction of 50% or more in the average number of migraine days per month, compared to 27% of those in the placebo group. Third, the fremanezumab group showed a greater change in the average number of days per month in which acute headache medication was used – a decrease of 2.1 days, compared to a decrease of 1 day in the placebo group.

“When we compared our results to those seen in other studies done in adults, the efficacy was the same,” said Hershey. “But the fact that we got a good response for fremanezumab in children and adolescents, and the placebo rate wasn’t as high as it has been in previous studies, was a good thing. It adds a new tool to the toolbox for providers to help younger people who live with migraine.”

Thanks to these results, the US Food and Drug Administration approved fremanezumab for use in the pediatric population in August 2025, and Health Canada approved it earlier this year.

A few caveats
Orr applauded the addition of fremanezumab to the therapeutic arsenal for pediatric migraine, and looks forward to future trials examining the efficacy of other drugs targeting CGRP or its receptor in younger people. But she said that the results, while “very exciting,” still call for a bit of caution.

“Recruitment is always super hard in pediatric trials. We just do not get enrollment like we do on the adult side,” she said. “And this study only has a third to one-quarter of the number of participants you’d see on the adult side. Given how high the placebo rate is with kids, even with significant results, there remains a question whether the study was big enough for us to be completely confident with the results. It would be great to see a trial with more participants get the same results.”

Further, while the most common adverse event with the drug was only mild to moderate injection-site erythema (redness of the skin), Orr was concerned that a three-month trial is not long enough to give an understanding of the full safety profile of fremanezumab in younger people.

“You can find CGRP all over the body. Animal studies show us that it has roles in growth, in metabolism, in the cardiovascular system, the uteroplacental unit, and in the immune axis,” she said. “Until we have long-term data, we don’t know if there may be any long-term side effects that we need to be concerned about.”

Hershey said he and his colleagues will be looking at long-term safety out to 12 months in the current participants, in an ongoing open-label extension of the trial. A similar open-label extension of a parallel trial of fremanezumab for kids with chronic migraine (15 or more headache days/month) is also underway. While that trial did not reach its endpoints, Hershey said viewing migraine as episodic versus chronic is an “artificial demarcation.”

“Migraine is really just one disease,” he said. “Patients don’t see a difference between 14 days and 16 days.” However, regulatory guidelines require trials for each subgroup.

That said, with the current results in hand, Hershey is heartened that fremanezumab, in conjunction with lifestyle modifications, can help kids better prevent debilitating headaches.

“The earlier we can teach children and adolescents how to manage their disease, the more likely we are that we can minimize the lifetime or long-term impact of living with migraine disease,” he said. “Healthy lifestyle habits, like a healthy diet, drinking enough water every day, and exercise, are a big part of that. But fremanezumab is now another tool we can use to help reduce headache days. And the more tools we have to help younger people living with migraine reduce those days, the better.”

Kayt Sukel is a freelance writer based in Kansas.

Image credit: ID 96867298 © Vadymvdrobot | Dreamstime.com

Reference
Fremanezumab in children and adolescents with episodic migraine.
Hershey et al.
N Engl J Med. 2026 Jan 15;394(3):243-52.