To assess the cardiovascular (CV) safety of fremanezumab in a large population of patients with episodic migraine (EM) and chronic migraine (CM) based on CV medical history and CV/cerebrovascular risk factors (CVRFs).

Understanding CV safety of medications targeting the calcitonin gene-related peptide (CGRP) pathway is important given the vasodilatory properties of CGRP. Fremanezumab, a fully-humanized monoclonal antibody (IgG2Δa) that selectively targets CGRP, has proven efficacy for the preventive treatment of migraine in adults.

This analysis of CV safety of fremanezumab included data from the 2 HALO studies (1 in EM, 1 in CM) and the FOCUS study (EM or CM patients with inadequate response to 2-4 classes of migraine preventive medications). In all 3 trials, patients were randomized 1:1:1 to quarterly fremanezumab, monthly fremanezumab, or placebo for 12 weeks. CV adverse events (CVAEs) were evaluated in patients with and without CV medical history and by number of CVRFs at baseline.

Among patients with CV medical history (fremanezumab, n = 325; placebo, n = 153), CVAEs occurred in similar, low proportions of patients across treatment groups (3%-6%); the most common CVAE was hypertension (0%-2%). Among patients without CV medical history (fremanezumab, n = 1,572; placebo, n = 792), CVAEs also occurred in similar, low proportions of patients across treatment groups (1%-2%). In total, 499 of 2,842 pooled patients had ≥2 CVRFs; of these, 66% had CV medical history. CVAEs were infrequent in patients with ≥2 or ≥3 CVRFs (0%-2%); no CVAEs were reported in patients with ≥4 CVRFs. No CV safety signals were identified.

This pooled analysis demonstrates a favorable CV safety profile for fremanezumab in patients with CV medical history or with ≥2 CVRFs. No CV safety signals were identified. These data support the strong safety profile of this preventive treatment targeting the CGRP pathway.