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
To evaluate the cardiovascular safety of fremanezumab in patients with episodic migraine (EM) and chronic migraine (CM). 
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. 
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.
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).
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.