Patients with a previous history of cardiovascular risks experienced similarly low number of cardiovascular events with treatment of fremanezumab compared with placebo.
Stephanie J. Nahas, MD
Data from a pair of studies revealed that treatment with fremanezumab (Ajovy; Teva Pharmaceuticals) is similarly effective in patients with higher-frequency episodic migraine (HFEM) and moderate-frequency episodic migraine (MFEM), as well as safe for patients with a previous history of cardiovascular (CV) risk.1,2
Both studies were presented at the 2021 American Academy of Neurology (AAN) Annual Meeting, April 17-22, by Stephanie J. Nahas, MD, associate professor, director, Headache Medicine Fellowship Program, Thomas Jefferson University. The data included in both abstracts were from 2 double-blind phase 3 trials (HALO EM, NCT02629861; FOCUS, NCT03308968), which randomized participants 1:1:1 to quarterly fremanezumab, monthly fremanezumab, or placebo for 12 weeks. The first included 1174 participants with episodic migraine (EM), 659 of which had MFEM and 515 with HFEM at baseline.1
From baseline, least-square mean (SE) reductions in monthly migraine days (MMDs) were significantly greater with fremanezumab versus placebo in the MFEM group (quarterly, –3.5 [standard evaluation (SE), 0.35]; monthly, –3.4 [SE, 0.22]; placebo, –1.5 [SE, 0.21]) and HFEM group (quarterly, –4.2 [SE, 0.35]; monthly, –4.7 [SE, 0.35]; placebo, –2.8 [SE, 0.35]; all P <.0009), indicating similar therapeutic gains.
Reductions in monthly headache days were also similar between the MFEM (quarterly, –3.0 [SE, 0.19]; monthly, –2.8 [SE, 0.19]; placebo, –0.8 [SE, 0.18]) and HFEM (quarterly, –3.5 [SE, 0.31]; monthly, –3.7 [SE, 0.31]; placebo, –1.8 [SE, 0.30]) groups. Proportions of participants with greater than 50% reduction in MMDs were also significantly higher with fremanezumab versus placebo in both groups (MFEM: quarterly, 51%; monthly, 50%; placebo, 25%; HFEM: quarterly, 38%; monthly, 42%; placebo, 21%; all P <.0005).
In the second presentation, Nahas and colleagues assessed the CV safety of fremanezumab in participants with EM and chromic migraine (CM) based on CV medical history and CV risk factors (CVRFs).2 Among participants with CV medical history (fremanezumab, n = 325; placebo, n = 153), CV adverse events (CVAEs) occurred in similar, low proportions across treatment groups (3% to 6%), the most common being hypertension (0% to 2%). In comparison with patients without CV medical history (fremanezumab, n = 1572; placebo, n = 792), CVAEs occurred in similar, low proportions of patients across treatment groups (1%-2%).
"This is important because we have theoretical concerns about antagonizing a system that is in-part responsible for vasoreactivity and cardiovascular and cerebrovascular autoregulation,” Nahas told NeurologyLive. “If you interfere with that, could you, in theory, be putting somebody at risk for a vascular acute event? Yes, you could.”
Participants with 2 or more CVRFs accounted for 499 of the 2842 pooled population. Of these 66% had CV medical history. Among participants with ≥2 or ≥3 CVRFs, CVAEs were infrequent (0%-2%). Additionally, no CVAEs were reported in participants with at least 4 or more CVRFs.
"It’s interesting that there were some participants with 4 or more cardiovascular risks and there were no cardiovascular adverse events in that group. That was perhaps a little bit surprising,” Nahas added.
Fremanezumab, an anti-calcitonin gene-related peptide (CGRP), was approved by the FDA in September 2018 for the prevention of migraine in adults. The drug was originally made available for administration via a prefilled syringe indicated for 1-time use. In January 2020, the FDA approved an autoinjector for the delivery of fremanezumab, joining Amgen’s erenumab (Aimovig), and Eli Lilly’s galcanezumab (Emgality) as the anti-CGRP agents on the market available for administration via autoinjector.3
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