Safety and Tolerability of Fremanezumab for Migraine Prevention

Vial and injection
Vial and injection
Researchers in large phase 2b and 3 studies found data that showed fremanezumab to be safe and effective preventive therapy in migraine treatment for adults.

The monoclonal antibody fremanezumab is generally well-tolerated and safe as a migraine prevention therapy in adults, with a level of efficacy and dosage flexibility that contributes to adherence and clinical outcomes, according to a study published in Headache.

Fremanezumab targets calcitonin gene-related peptide, a neuropeptide involved in migraine pathophysiology. Researchers assessed immunogenicity and adverse events of this pooled analysis of fremanezumab safety data taken from 4 placebo-controlled phase 2b and 3 studies of patients with chronic or episodic migraine experiencing >4 migraine days per month. The studies were multicenter, 16-week, randomized, placebo-controlled, double-blind, and parallel-group, and included a screening visit, 28 days of pretreatment for baseline, and 12 weeks of treatment with final evaluation 4 weeks postfinal dose.

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Of the 2566 participants included across all studies, 1704 were randomly assigned to receive fremanezumab and 862 to receive placebo, and 2563 total participants were treated. The most common reasons for discontinuation were participant withdrawal (n=78), participants lost to follow up (n=60), and adverse events (n=50). Adverse events were primarily mild to moderate and were experienced by 48% to 69% of participants across all groups, with injection site reactions being the most common. Rates of adverse events were significantly higher in the fremanezumab groups but were similar to the overall population in those who also received concomitant preventative medication. The mean (standard deviation) exposure duration was 83.8 (13.6) days for fremanezumab, with a total 390.4 patient years of exposure and a maximum of 181 days of exposure. Two deaths unrelated to the study drug occurred, 1 due to chronic obstructive pulmonary disease and 1 due to an intentional diphenhydramine overdose. Rates of adverse cardiovascular events, abnormal liver function, and hypersensitivity were similar between all groups and were uncommon.

Study investigators conclude, “This pooled safety analysis demonstrates that fremanezumab, a monoclonal antibody that blocks [calcitonin gene-related peptide], is generally safe and well-tolerated preventive therapy for migraine in adults. The safety profile of fremanezumab, combined with its efficacy and flexibility of dosing, has the potential to improve adherence and clinical outcomes.”

Please see the original reference for a full list of authors’ disclosures.


Silberstein SD, McAllister P, Ning X., et al. Safety and tolerability of fremanezumab for the prevention of migraine: a pooled analysis of phases 2b and 3 clinical trials [published online April 12, 2019]. Headache. doi: 10.1111/head.13534