Cardiovascular Safety of Fremanezumab in Patients with Episodic and Chronic Migraine: A Pooled Analysis of Phase 3 Studies
Stephanie J. Nahas1, Yoel Kessler2, Xiaoping Ning2, Joshua M. Cohen2, Verena Ramirez Campos2, Ronghua Yang2, Stephen D. Silberstein1
1Jefferson Headache Center, Thomas Jefferson University, 2Teva Pharmaceuticals Industries
Objective:
To evaluate the cardiovascular safety of fremanezumab in patients with episodic migraine (EM) and chronic migraine (CM). 
Background:
Understanding the cardiovascular safety of medications targeting the calcitonin gene-related peptide (CGRP) pathway is critically important given the vasodilatory properties of CGRP. Fremanezumab, a fully-humanized monoclonal antibody (IgG2Δa) that selectively targets CGRP, has been studied in three phase 3 trials. 
Design/Methods:
This analysis of the cardiovascular safety and tolerability of fremanezumab included data from the 2 HALO studies (one in EM and one in CM), and the FOCUS study in patients with EM or CM and prior inadequate response to 2-4 classes of preventive medications. In all 3 trials, patients were randomized 1:1:1 to receive subcutaneous injections of fremanezumab quarterly (Months 1/2/3: EM or CM, 675mg/placebo/placebo), fremanezumab monthly (Months 1/2/3: EM, 225mg/225mg/225mg; CM, 675mg/225mg/225mg) or matched placebo over 12 weeks. Cardiovascular adverse events (AEs) were evaluated in patients with and without cardiovascular medical history.
Results:
Among patients with cardiovascular medical history (quarterly fremanezumab [675mg], n=167; monthly fremanezumab [225mg/225mg/225mg], n=64; monthly fremanezumab [675mg/225mg/225mg], n=94; placebo, n=153), cardiovascular AEs occurred in similar, low proportions of patients across treatment groups (4%, 6%, 6%, and 3% respectively). Among patients with cardiovascular medical history, the most common cardiovascular AE was hypertension (quarterly fremanezumab [675mg], 2%; monthly fremanezumab [225mg/225mg/225mg], 0%; monthly fremanezumab [675mg/225mg/225mg], 1%; placebo, <1%). Among patients without cardiovascular medical history (quarterly fremanezumab [675mg], n=776; monthly fremanezumab [225mg/225mg/225mg], n=337; monthly fremanezumab [675mg/225mg/225mg], n=459; placebo, n=792), cardiovascular AEs also occurred in similar, low proportions of patients across treatment groups (2%, 1%,2%, and 2%, respectively).
Conclusions:
Pooled data from three phase 3 trials indicate that treatment with fremanezumab over 12 weeks has a favorable cardiovascular safety profile, even in patients with a cardiovascular medical history, with no safety signals detected.