GammaCore nVNS Device Offers Versatile Option in Migraine and Cluster Headache

Stephen D. Silberstein, MD, professor of neurology, and director, Jefferson Headache Center, Thomas Jefferson University

Stephen D. Silberstein, MD

A recent clinical update suggests that the combination of the safety and tolerability of electroCore’s non-invasive vagus nerve stimulation (nVNS) device, gammaCore, with the identified clinical and mechanistic evidence support its use as a first-line treatment for patients with cluster headache as both an acute and preventive therapy. Additionally, the literature review suggests that nVNS is also an effective option for acute migraine treatment and a practical option for migraine prevention.¹

Conducted by Stephen D. Silberstein, MD, professor of neurology, and director, Jefferson Headache Center, Thomas Jefferson University, and colleagues, the narrative review included the findings from mechanistic studies and their possible relationships to the clinical effects of nVNS, as well as safety data, representing the largest dataset a neuromodulation device (n = 1091).

“Over the past several years, the basic science and clinical evidence from studies completed across the United States and Europe have shown us not only the clinical benefit of nVNS but how and why it may be working in those patients,” Silberstein said in a statement.² “The interplay and overlap of the many ways nVNS affects the brain supports its ability to be used as a preventive and acute treatment for both cluster and migraine headache. Neuromodulation is a tool that we feel should be available to our cluster and migraine headache patients who need it.”

The reviewing group identified 4 core areas providing mechanistic explanations for the device’s efficacy: Effects on autonomic nervous system functions; inhibition of cortical spreading depression; neurotransmitter regulation; and nociceptive modulation.

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The effects on the autonomic nervous system are supported by the functional MRI findings in humans that imply the device may modulate the trigeminal autonomic reflex through a network including the hypothalamus, the spinal trigeminal nuclei, the left pontine nucleus, and the parahippocampal gyrus. Additionally, findings from rat models of migraine, cluster headache, ischemic stroke, and recurrent headache are suggestive of the gammaCore device’s cortical spreading depression inhibition, regulation of neurotransmitters, and nociceptive modulation.

Clinical trial evidence from 2 randomized, double-blind trials—ACT1 (NCT01792817) and ACT2 (NCT01958125)—a meta-analysis, and real-world assessment support the device’s efficacy and safety.^3,4 In migraine, the PRESTO (NCT02686034), EVENT (NCT01667250), and PREMIUM (NCT00355056) studies are similarly positive, and another, PREMIUM II (NCT03716505) is nearing completion. With regard to the overall safety profile, there were serious treatment-related adverse events (AEs) reported in any of the controlled clinical trials of nVNS for cluster headache (including PREVA) or migraine.

“We are pleased with the scientific review and clinical recommendations made by the authors of this clinical update and hope that these recommendations, which we believe support the use of gammaCore (nVNS) in the treatment of both cluster and migraine headache, will help drive awareness of this novel technology by physicians and patients alike,” said Peter Staats, MD, chief medical officer, electroCore, in a statement.²

Clinically, Silberstein et al. identified that it offers advantages for patients in that it is usable at any stage in the course of treatment, as monotherapy or in tandem without risk of drug interactions, and unrestricted for up to 24 stimulations per day. They noted that its “unique level of control” provides patients with a safe, flexible, and effective non-pharmacologic option for treatment.

They also pointed to the possibility of its use during pregnancy and in adolescent patients with migraine, though acknowledged the need for further evidence. The nVNS device is also being tested for controlling the vestibular symptoms in patients with vestibular migraine.

“The growing understanding of the first line role of nVNS for the treatment of cluster headache and its ability to be used acutely and preventively in migraine and cluster headache is a credit to the quality of the basic science and clinical trials that support these treatment recommendations,” review co-author Eric Liebler, senior vice president, Neurology, electroCore, said.

REFERENCES

1. Silberstein SD, Yuan H, Najib U, et al. Non-invasive vagus nerve stimulation for primary headache: A clinical update. Cephalagia. Published online July 27, 2020. doi: 10.1177/0333102420941864.

2. electroCore Announces Non-Invasive Vagus Nerve Stimulation Clinical Update Publication in Cephalalgia [press release]. Basking Ridge, NJ. electroCore. Published July 28, 2020. Accessed August 11, 2020. https://www.globenewswire.com/news-release/2020/07/28/2068686/0/en/electroCore-Announces-Non-Invasive-Vagus-Nerve-Stimulation-Clinical-Update-Publication-in-Cephalalgia.html

3. de Coo IF, Marin JC, Silberstein SD, et al. Differential efficacy of non-invasive vagus nerve stimulation for the acute treatment of episodic and chronic cluster headache: A meta-analysis. Cephalalgia. 2019; 39: 967—977. doi: 10.1177/0333102419856607.

4. Marin J, Giffin N, Consiglio E, McClure C, Liebler E, Davies B. Non-invasive vagus nerve stimulation for treatment of cluster headache: early UK clinical experience. J Headache Pain. 2018;19(1):114. Published 2018 Nov 23. doi:10.1186/s10194-018-0936-1.