ElectroCore’s Noninvasive Vagus Nerve Stimulation Evaluated for Treatment of Acute Stroke

February 9, 2022—ElectroCore, Inc. announced that data on the possible role of noninvasive vagus nerve stimulation (nVNS) in the acute treatment of stroke were presented from three abstracts at the American Heart Association’s 2022 International Stroke Conference held February 9-11 in New Orleans, Louisiana.

The TR-VENUS evaluated nVNS for the acute treatment of ischemic or hemorrhagic stroke and NOVIS studied nVNS in acute ischemic stroke. The third study analyzed the effect of nVNS in hemorrhagic brain injury and permanent ischemic stroke in rats.

According to the company, the randomized, sham-controlled, multicenter TR-VENUS study was conducted at nine academic centers in Turkey. The intent-to-treat (ITT) population included 69 patients (61 ischemic stroke and eight intracerebral hemorrhage) distributed into three treatment arms: sham (n = 25); standard-dose nVNS (seven stimulations in 1 hour; n = 19); and high-dose nVNS (seven stimulations in hour 1 and hour 5; n = 25). Every patient in the ITT population received all prespecified treatment stimulations per protocol and 97% of all randomized subjects in the study received their first stimulation < 6 hours from stroke onset.

The study met its primary objective with the composite primary safety endpoint being consistent across the three treatment arms indicating that nVNS was able to be administered safely in this acute stroke population.

The study also met all secondary safety and feasibility endpoints. Relative infarct growth, measured by diffusion weighted imaging, in the high dose nVNS group was lower than in the sham group against baseline (63.3% vs 185.8%; P = .05).

Murat Arasava, MD, who is Professor of Neurology at the Hacettepe University in Ankara, Turkey, is one of the primary investigators of the TR-VENUS study.

“We are pleased to have successfully completed this first trial of nVNS as a possible treatment for acute stroke and believe our data suggests that nVNS may be safe and feasible in both ischemic and hemorrhagic stroke,” commented Professor Arasava in the company’s press release. “The efficacy signal suggested by the reduction in relative infarct growth rate in the ischemic population, which needs to be confirmed in larger studies, clearly provides the basis for additional research to further define the role for nVNS for the acute treatment of stroke.”

The prospective NOVIS randomized clinical trial with blinded outcome assessment is being conducted at the Leiden University Medical Center in Leiden, The Netherlands. In the trial, 150 patients with ischemic stroke are being randomly allocated 1:1 either to nVNS for 5 days in addition to standard treatment or to standard treatment alone. The primary endpoint is the final infarct volume on day 5 assessed with magnetic resonance imaging.

According to the company, the NOVIS study features a greater number of stimulations in 5 days than the TR-VENUS study and advanced imaging endpoints, including measurement of the penumbra, that should provide additional insight and clarity surrounding the role of nVNS for the acute treatment of ischemic stroke.

Anne van der Meij, MD, with the Leiden University Medical Center, who presented the poster at the International Stroke Conference, commented in the company’s press release, “Our study is now more than 50% enrolled and our efficacy endpoints may provide greater definition, and possibly confirmation, of the efficacy of nVNS for the acute treatment of ischemic stroke.”

The preclinical study of the use of nVNS in rats, was conducted by Ilknur Ay, MD, at the Athinoula A. Martinos Center for Biomedical Imaging in Boston, Massachusetts. Dr. Ay is with the Massachusetts General Hospital and Harvard Medical School in Boston.

The company stated that the findings support previous evidence that nVNS may have therapeutic potential in ischemic stroke. The lack of adverse events in two different validated models of intracerebral hemorrhage in rats shown in this study suggests that nVNS could be safely administered as early as an ambulatory setting before the stroke etiology (ischemic versus hemorrhagic) has been determined.

Eric Liebler, Senior Vice President of Neurology for ElectroCore, commented in the company’s press release, “We congratulate all of the investigators, patients, and sites that have first in human study suggesting a role for nVNS in treatment of acute stroke.”

He continued, “If effective, nVNS would represent a breakthrough treatment that could be safely deployed much earlier, more safely, and more easily than current stroke treatments. As time to treatment is considered one of the most critical factors in the acute treatment of stroke, the ability to treat as early as in an ambulatory setting, before the type of stroke (ischemic or hemorrhagic) is confirmed by imaging, would represent a significant advance in the treatment of stroke.”

Finally, Mr. Liebler advised, “We look forward to the anticipated full publication of the TR-VENUS study in a peer reviewed journal later this year and the completion of the NOVIS study in 2023.”

ElectroCore’s handheld GammaCore nVNS therapy is currently approved as an adjunctive therapy applied at the neck to treat migraine and cluster headache through the utilization of a mild electrical stimulation that passes through the skin to the vagus nerve.

The GammaCore nVNS is FDA cleared in the United States for adjunctive use for the preventive treatment of cluster headache in adult patients; the acute treatment of pain associated with episodic cluster headache in adult patients; and the acute and preventive treatment of migraine in adolescent (age ≥ 12 years) and adult patients; and paroxysmal hemicrania and hemicrania continua in adult patients.

In Europe, GammaCore has CE Mark approval for the acute and/or prophylactic treatment of primary headache (migraine, cluster headache, trigeminal autonomic cephalalgias and hemicrania continua) and medication overuse headache in adults, advised ElectroCore.