Regulatory Decision Summary for Ajovy

This Supplemental New Drug Submission (SNDS) was submitted to propose the following Level I change for the addition of the following indication in the pediatric population:

Ajovy (fremanezumab) is indicated for the prevention of episodic migraine in pediatric patients aged 6 years and older, weighing at least 45 kg.

Pediatric migraine can be a major cause of disability in Canada and elsewhere, and there are no approved treatments for pediatric migraine prevention in Canada.

The efficacy of Ajovy (fremanezumab) in pediatric patients with a clinical diagnosis of episodic migraine was evaluated in one Phase 3, multicentre, randomized, double-blind, placebo-controlled trial of 3 months’ duration in patients having episodic migraine.

The trial included participants aged 6 through 17 inclusive. The primary efficacy endpoint was the mean change from baseline in monthly average number of migraine days during the 12-week period after the first dose of trial drug. The least squares (LS) mean (95% confidence interval [CI]) change from baseline in monthly average number of migraine days during the 12-week double-blind period was -1.4 (-2.22, -0.67) days in placebo group and -2.5 (-3.22, -1.72) days in fremanezumab group. The LS mean difference of -1.0 days (95% CI: -1.90, -0.16) between placebo and fremanezumab groups was statistically significant for the full analysis set. From a clinical standpoint, the magnitude of the treatment effect was modest, but consistent with what has been observed in adult episodic migraine trials. Key secondary endpoints supported the primary endpoint.

Although the pivotal trial included pediatric migraine patients weighing 45 kg or more and those weighing less than 45 kg, the sponsor indicated that no appropriate strength presentation was available for patients weighing less than 45 kg.

Across the pivotal 12-week placebo-controlled trial (TV48125-CNS-30083) and the ongoing open-label extension (TV48125-CNS-30084), the most frequently reported adverse events were injection site reactions (e.g., erythema, pain, swelling), nasopharyngitis, and headache. These events were predominantly mild to moderate in severity and self-limiting. No deaths or treatment-related serious adverse events were reported.

However, limitations remain in the characterization of long-term safety, particularly in children under 12 years of age, due to small sample sizes and limited exposure duration. In addition, non-clinical data suggest a potential role for calcitonin-gene-related peptide (CGRP) in bone growth. While no clinically meaningful trends in growth or pubertal development were observed in the interim data, there was limited assessment of these endpoints. As such, the long-term impact of CGRP inhibition on skeletal development remains uncertain. The Product Monograph includes precautionary language advising growth monitoring in pediatric patients receiving treatment for episodic migraine.

Overall, the benefit-risk profile was favourable for Ajovy (fremanezumab) 225 mg for the approved indication when used under the conditions of use recommended in the approved Product Monograph. Therefore, a Notice of Compliance (NOC) was recommended.

An updated Risk Management Plan (RMP) for Ajovy was reviewed by Health Canada and considered acceptable.

Following review and requested revisions, the final labelling and Product Monograph were considered acceptable.

For further details about Ajovy, please refer to the Product Monograph, approved by Health Canada and available through the Drug Product Database.