Andrew Hershey, MD, discusses latest phase 3 results of fremanezumab-vfrm for pediatric episodic migraine

Recent phase 3 data published in The New England Journal of Medicine provide new evidence supporting the use of fremanezumab-vfrm (AJOVY; Teva) for migraine prevention in children and adolescents. In the randomized, placebo-controlled SPACE trial, fremanezumab significantly reduced monthly migraine days and headache days of at least moderate severity compared with placebo in patients aged 6 to 17 years with episodic migraine, with a safety profile consistent with prior adult studies.^1,2

The findings supported FDA approval of fremanezumab for preventive treatment in pediatric patients who meet weight criteria, marking an important regulatory and clinical milestone in a population with limited evidence-based preventive options.³

To better understand the clinical implications of these results, we spoke with Andrew D. Hershey, MD, PhD, lead study author and director of neurology at Cincinnati Children’s Hospital Medical Center.

Contemporary Pediatrics: What do you see as the key clinical takeaway from the SPACE trial results in terms of migraine prevention for children and adolescents?

Andrew Hershey, MD, PhD: The key takeaway being the first of a class of 4 that's been shown to be very efficacious and safe in adults, and to add this to children and adolescents for the prevention of headaches due to migraine is a key essential component and additional tool in our toolbox to help these children and adolescents.

Contemporary Pediatrics: The study showed a meaningful reduction in monthly migraine and headache days compared with placebo. How should physicians interpret the magnitude of benefit seen here when deciding whether to initiate preventive therapy?

Hershey: It's hard to determine the magnitude of the benefits in a controlled, blinded study like this, because it wasn't a comparative study, meaning it wasn't comparing it to other treatments or other medications, but what can be significantly said is that it did statistically separate from placebo, and the amount of response compared to comparable adult studies was very equivalent. So, we can use and draw upon a lot of the adult information that showed this really is a very effective medication for the prevention of headaches due to migraine.

Contemporary Pediatrics: Nearly half of patients achieved a 50% or greater reduction in monthly migraine days. Why is that responder rate important for pediatric practice, and how does it compare with existing preventive options?

Hershey: So the 50% responder rate is somewhat of an artificial number that's been put into place for studies and purposes. From a kid's perspective, from an adult's perspective, they really just want their headaches to go away. So oftentimes, a better key indicator is, "Are you dropping down to less than one headache a week?" Although that wasn't a primary but a secondary outcome of the study, from a clinical perspective, what's meaningful to the families is to get to that point. So, we can piece together the results of this study, including the absolute reduction in days with headaches that were consistent with migraine, days that are just headache days, which, in essence, were really migraine, or the number of patients that had a 50% or greater reduction in their headache numbers. So, these are all used statistically to identify an efficacious medication. But in the clinical perspective, what a patient really wants is their headaches to go away, or at least get to the point that they're at a level that they're tolerable.

Contemporary Pediatrics: Safety is always top of mind in pediatric neurology. What did the SPACE trial tell us about the safety and tolerability of CGRP-targeted therapy in this younger population?

Hershey: Well, similar to adults, it was very safe, also very similar to adults, there was a little bit of some type of irritation, erythema at the injection site, which is understandable whenever there's an injection. But other than that, it was very safe and very well tolerated, and that's been the experience over the last 5 plus years in the use of these compounds in adults. So it's very reassuring to see that nothing new is developing in kids, especially across these developmental ages.

Contemporary Pediatrics: With FDA approval now in place for eligible pediatric patients, how do you anticipate these data changing real-world treatment pathways for children and adolescents with episodic migraine?

Hershey: So, the FDA approval has been around for a while, so we've had a little bit of experience with how it's come through. I think it does add a tool to the toolbox. Ultimately, unfortunately, the way medicine works today is through the pre-approval process from insurance companies. So, oftentimes, they do still require, including in adults, that the older medications be tried first. I only bring that up because I was also part of an editorial that was published in Headache that covered all ages, which really said this class of medication should be considered first line. Oftentimes first line can be medically indicated and scientifically indicated, but the insurance carriers sometimes restrict it from being that. Where I think it will fall in line is that inevitably, because people do prefer, especially if there's a needle involved, they want to try a pill based treatment, potentially first, but if they are not effective or if adherence is a problem, or they do want to try something new, then this is really the one that we do have available that's approved by the FDA. So I think, and I'm a strong proponent, that the patient's choice needs to drive the decision more than a doctor telling them what to do. So, I do see that, especially in a busy world, if you can give yourself a shot once a month, it's more or equally effective as taking a pill every day. A lot of patients choose that route. We do have some nuances. It's the first approval was for 0 to 15 headache days per month. We've argued with some insurance companies that if you have 16 days per month, it should still be used, and it's not indicated for that because of the arbitrary nuance that was developed several years ago that split the disease migraine in half at 15 days, but theoretically it should be used as the disease is migraine across all the frequencies.

References

1. Teva. AJOVY® (fremanezumab-vfrm) Significantly Reduced Monthly Migraine and Headache Days in Children and Adolescents with Episodic Migraine Compared to Placebo in the SPACE Trial; Results Published in New England Journal of Medicine. Teva. January 14, 2026. Accessed January 15, 2026. https://www.tevapharm.com/news-and-media/latest-news/ajovy-fremanezumab-vfrm-significantly-reduced-monthly-migraine-and-headache-days-in-children-and-adole/
2. Hershey AD, Szperka CL, Barbanti P, et al. Fremanezumab in Children and Adolescents with Episodic Migraine. New England Journal of Medicine. 2026;394(3):243-252. doi:https://doi.org/10.1056/nejmoa2504546
3. Fitch J. FDA approves fremanezumab-vfrm for migraine prevention in children aged 6 years, older. Contemporary Pediatrics. August 5, 2025. Accessed January 15, 2026. https://www.contemporarypediatrics.com/view/fda-approves-fremanezumab-vfrm-for-migraine-prevention-in-children-aged-6-years-older