No CV safety signals with fremanezumab for migraine treatment

Patients using the CGRP* blocker fremanezumab for migraine treatment need not worry about cardiovascular (CV) safety of the drug, as pooled data from three phase III trials showed no safety signals for CV events with the treatment, even in those with a CV medical history.  

“Understanding the CV safety of medications targeting the CGRP pathway is critically important given the vasodilatory properties of CGRP,” said lead author Dr Stephanie Nahas of Thomas Jefferson University in Philadelphia, Pennsylvania, US, who presented the study during the 2020 AAN Virtual Meeting.

CGRP receptors are also found in the heart and the blood vessels, apart from the central and peripheral nervous systems, she pointed out.

“[Given that] CGRP may act as a potent vasodilatory safeguard during cerebral and cardiac ischaemia, continuous blockade of CGRP raises concerns that transient ischaemic events could transform into major infarcts,” explained Nahas.  

To address the CV safety of fremanezumab, Nahas and colleagues pooled data of 2,842 patients from three phase III studies: two HALO studies (one on episodic migraine and the other on chronic migraine) and the FOCUS study, which enrolled patients with episodic or chronic migraine. In all trials, patients were randomized in a 1:1:1 ratio to receive quarterly (675 mg) or monthly (225 mg**) subcutaneous injections of fremanezumab or a matching placebo over 12 weeks. [AAN 2020, abstract S8.004]

Among the patients with a CV medical history (n=478), CV adverse events (AEs) occurred at similarly low rates across all treatment groups (4 percent, 6 percent, and 3 percent for quarterly and monthly fremanezumab, and placebo, respectively).

Similarly, the rates of CV AEs were also low and comparable across all treatment groups among those without a CV medical history (n=2,364; 2 percent, 1 percent, 2 percent, and 2 percent for quarterly fremanezumab, monthly fremanezumab for episodic and chronic migraine, and placebo, respectively).

The most common CV AEs reported across both subgroups of patients with or without CV medical history were hypertension, palpitations, and increased heart rate, reported Nahas.

“These results demonstrate that treatment with fremanezumab over 12 weeks has a favourable CV safety profile, even in patients with a CV medical history, with no safety signals detected, based on pooled data from three phase III trials,” she concluded.  

Fremanezumab is a fully-humanized monoclonal antibody which selectively targets the CGRP pathway. It has been approved by the US FDA for preventive treatment of migraine in adults. Development for preventive treatment of cluster headache is currently ongoing.