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. 2022 Jul;42(8):769-780.
doi: 10.1177/03331024221076485. Epub 2022 Mar 25.

Safety and tolerability of fremanezumab in patients with episodic and chronic migraine: a pooled analysis of phase 3 studies

Hans Christoph Diener  1 , Peter McAllister  2 , Tim P Jürgens  3 , Yoel Kessler  4 , Xiaoping Ning  4 , Joshua M Cohen  4 , Verena Ramirez Campos  4 , Steve Barash  4 , Stephen D Silberstein  5
Affiliations

Safety and tolerability of fremanezumab in patients with episodic and chronic migraine: a pooled analysis of phase 3 studies

Hans Christoph Diener et al. Cephalalgia. 2022 Jul.

Abstract

Background: Fremanezumab, a fully humanized monoclonal antibody that selectively targets calcitonin gene-related peptide, has demonstrated efficacy for preventive treatment of episodic and chronic migraine. Since calcitonin gene-related peptide is expressed within the cardio- and cerebrovascular system and may have cardioprotective effects, it is critical to understand the cardio- and cerebrovascular safety of fremanezumab.

Methods: This was a pooled analysis of three randomized, double-blind, placebo-controlled, phase 3, 12-week trials in which patients with episodic migraine or chronic migraine received quarterly fremanezumab, monthly fremanezumab, or placebo. Incidences of overall and serious adverse events were analyzed. Cardio- and cerebrovascular adverse events (CVAEs) were analyzed in subgroups stratified by cardio- and cerebrovascular medical history, cardiovascular risk factors (CVRFs), and use of cardio- and cerebrovascular medications or triptans.

Results: Two thousand, eight hundred and forty-two patients were included in the study. Overall (58-65%) and serious adverse events (<1-2%) occurred in similar proportions across fremanezumab and placebo groups. CVAEs were infrequent, regardless of cardio- and cerebrovascular medical history (2-6%). CVAEs occurred in low, similar proportions of patients with CVRFs and those using cardio- and cerebrovascular medications or triptans. No cardio- and cerebrovascular signals were identified.

Conclusion: Fremanezumab demonstrated a favorable overall and cardio- and cerebrovascular safety profile in more than 2800 patients with episodic migraine or chronic migraine, regardless of cardio- and cerebrovascular medical history, CVRFs, or medication use.Trial Registrations: NCT02629861 (HALO EM, https://clinicaltrials.gov/ct2/show/NCT02629861), NCT02621931 (HALO CM, https://clinicaltrials.gov/ct2/show/NCT02621931), NCT03308968 (FOCUS, https://clinicaltrials.gov/ct2/ show/NCT03308968).

Keywords: calcitonin gene-related peptide; cardiovascular; fremanezumab; safety.

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Conflict of interest statement

Declaration of conflicting interests: The authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: HCD received honoraria for participation in clinical trials, contribution to advisory boards, or oral presentations from: Alder, Allergan, Amgen, electroCore, Ipsen, Lilly, Medtronic, Novartis, Pfizer, Teva Pharmaceuticals, and Weber & Weber. electroCore provided financial support for research projects. The German Research Council, the German Ministry of Education and Research, and the European Union support his headache research. PM is an employee of the New England Institute for Neurology and Headache. He is an independent contractor and part of speaker bureaus at Teva Pharmaceuticals, Amgen, and Allergan. TPJ received honoraria for contribution to advisory boards or oral presentations from: Allergan, Desitin, Hormosan, Novartis, Lilly, Sanofi, and Teva Pharmaceuticals. His research is supported by Gemeinsame Bundesausschuss – Innovationsfonds and EFRE. YK, XN, VRC, and SB are employees and/or stockholders of Teva Branded Pharmaceutical Product R&D, Inc. JMC is a former employee of Teva Branded Pharmaceutical Product R&D, Inc. SDS provides consultation to Alder, Allergan, Amgen, Autonomic Technologies, Avanir, Curelater, Inc., Depomed, Dr. Reddy’s Laboratories, Ensured, Inc., electroCore, eNeuraTherapeutics, INSYS Therapeutics, Lilly, Supernus Pharmaceuticals, Inc., Teva Pharmaceuticals, Theranica, and Trigemina, Inc.

Figures

Figure 1.
Figure 1.
Systolic (a) and diastolic (b) blood pressure values by hypertension status from the long-term safety study. SBP: systolic blood pressure; DPB: diastolic blood pressure.
See this image and copyright information in PMC

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