Nearly everyone has had a headache, but migraines are a different species. They can be terribly disabling, with throbbing pain, nausea and other symptoms lasting from hours to days. In some cases, vision is also impaired. The search for therapies that effectively control migraine has fueled countless biomedical endeavors. To that end, Neurolief Ltd., of Netanya, Israel, reported new data showing significant relief from migraine following treatment with Relivion, the first noninvasive neuromodulation system to target two major nerves where migraines originate.
The prospective, double-blind, parallel-group clinical trial evaluated 55 migraine sufferers randomized to treatment with Relivion or sham neuromodulation. After two hours of treatment, 76% of patients in the treatment group achieved headache relief vs. 31% in the control group. Moreover, 43% of subjects with severe or moderate pain prior to treatment reported being pain-free two hours after treatment, compared with less than 11% of controls. No adverse events were reported in either group. The results were presented at the American Headache Society's annual conference in Philadelphia on July 13.
Pivotal study underway
Stewart Tepper, professor of neurology at Dartmouth University's Geisel School of Medicine, who presented the findings, called the study results "significant" for migraine sufferers who want to avoid more risky, implantable treatment options or medication. The study was used to secure CE marking for Relivion, which was received July 2.
The CE mark allows Relivion to be sold and distributed as an over-the-counter therapy within the European Union and other countries that accept the designation. A pivotal study for migraine treatment is currently underway at nine sites, including four in the U.S., and Neurolief expects to file for FDA clearance near the end of this year. "The company is currently working on a rollout plan, which will include at a later stage a rollout in the U.S. based on FDA clearance in mid-2020," Shmuel Shany, Neurolief's co-founder and CEO, told BioWorld MedTech. He added that the company has "detailed plans" for market entry in all major global markets, including China, Japan, South Korea and India.
According to a 2018 National Center for Biotechnology Information analysis, roughly 1 in 6 Americans and 1 in 5 women self-reported migraine or severe headaches over a three-month period, and the problem consistently ranks as the fourth or fifth most common reason for emergency room visits. The Migraine Research Foundation puts the annual costs in health care dollars and lost productivity at $36 billion. Worldwide, migraine is the third most prevalent diagnosis reported.
How it works
Relivion's relief comes via an adjustable, electronic headset, which delivers pulses to six branches of the occipital and trigeminal nerves by means of adaptive output channels. The two nerves then relay stimulation directly to the brainstem. The cloud-enabled system connects to a mobile phone app that assimilates the activity data, using predictive analytics to refine and personalize treatment over time.
"The Relivion is a comfortable, noninvasive wearable therapy that can be self-administered," Tepper said. "More importantly, it comes without side effects or contraindications associated with medication, targets the major neural pathways responsible for migraine pain and can learn to deliver personalized treatment to individuals to better treat acute migraine attacks."
Shany noted that patients can sync and share data with their doctors to improve monitoring and outcomes. The device is intended as a first-line treatment for migraine or in combination with other therapies.
Physician response to Relivion has been very positive, Shany said. "It's important to note that the current exceptional results are based on the general protocol, and we expect results to improve significantly as the Relivion's personalized medicine component is rolled out," he added. "The fact that the Relivion is the only device on the market that can modulate both the occipital and trigeminal nerves concurrently, six nerve branches with three channels, leads to exceptional clinical results and allows the device to be very comfortable to use."
There are other available noninvasive neurostimulation systems for migraine, but none of those target the occipital nerve, where most migraines originate. FDA-cleared options include the Cefaly headband, from Cefaly U.S. Inc., Neuronetics Inc.'s Neurostar transcranial magnetic stimulator and the Gammacore system, manufactured by Electrocore Inc. The newest competitor, Theranica Bio-Electronics Ltd.'s Nerivio Mitra, a smartphone-operated, electromedical device, received 510(k) clearance in May.
Pay as you go
Neurolief hopes Relivion will be the answer to migraine sufferers' prayers, but do so without putting a big hole in users' pockets. The goal, Shany said, is to be able to market it as an affordable, pay-as-you go or bundle package. "In the EU, patients can purchase credits via the mobile app, and each use payment provides 48 hours of unlimited usage," he explained. The company plans to follow a similar pricing model in the U.S., working with insurers to improve patient access.
With a CE mark in hand and U.S. clearance on the horizon, Neurolief is already looking beyond migraine relief to broader applications for Relivion. Future indications for the technology include migraine prevention, depression, insomnia, attention deficit hyperactivity disorder and other chronic pain and neurological disorders.
Interim results from a feasibility study assessing Relivion's use in depression have been "very positive in terms of safety and efficacy," Shany said. "We plan to begin clinical studies evaluating efficacy of the Relivion for treatment of depression in 2020."