Remote Electrical Neuromodulation Displays Superiority in Significantly Reducing Migraine Days

Stewart J. Tepper, MD

Recent data from a double-blind randomized sham-controlled clinical trial (NCT04828707) of Nerivio, Theranica’s remote electrical neurostimulation (REN) device, showed superiority in efficacy and safety compared to placebo as a treatment for migraine prevention in patients with episodic and chronic migraine.¹

In the primary endpoint, REN was superior to placebo in the reduction of migraine days per month from baseline, with a mean change of -4.0 (±0.4) days (placebo, -1.3 (±0.4); gain = -2.7; P = .00002). Notably, in subgroup analyses, the significance was maintained in episodic (-3.2 vs -1.0; P = 0.003) and chronic (-4.7 vs -1.6; P = .001) migraine, separately.

These findings were presented as an abstract presentation in the advances in migraine therapeutics session at the 2023 American Academy of Neurology (AAN) Annual Meeting, April 22-27, in Boston, Massachusetts, by lead author Stewart J. Tepper, MD, professor of neurology at the Geisel School of Medicine at Dartmouth and director of the Dartmouth Headache Center at Dartmouth Health.

Investigators conducted a prospective, randomized, double-blind, sham-controlled, multi-center trial, where patients were randomized in a 1:1 ratio. The trial consisted of a 4-week baseline observation period and an 8-week double-blind intervention period where participants used either REN or sham stimulation every other day. Participants self-reported their symptoms daily throughout the study in an electronic diary.

Among the 248 participants randomized in the trial (active, n = 128, placebo, n = 120), 179 qualified for the mortified intention-to-treat (mITT) analysis (active, n = 95; placebo, n = 84). In patients using a preventative in addition to REN, a significant reduction in migraine days was maintained (-3.5 vs -1.5; P = .03) and as well as sustained in patients who had no additional prophylaxis (-4.5 vs -1.5; P = .00016). In both active and placebo groups, there were no reports of serious device-related adverse events.

In February 2023, Nerivio received FDA approval as a dual-use acute and preventive treatment for migraine with or without aura in patients 12 years of age or older and was supported by the results from the double-blind randomized clinical trial.² The device is worn on the upper arm at the onset of a migraine attack and utilizes REN to trigger an endogenous analgesic mechanism, known as conditioned pain modulation.

The nonpharmalogical treatment is the first FDA-cleared smartphone-controlled prescription wearable device for acute migraine treatment of episodic or chronic migraine in people 12 years and older. The device received another prior approval in October 2020 but at the time, was only approved for patients aged 18 years and older.³ In May 2019, its initial de novo clearance was granted for the acute treatment of migraine with or without aura in adults.⁴

Following that, in January 2021, Nerivio received clearance as an acute treatment for migraine in the same patient population, based on a single-arm, multicenter study. The study included 45 participants with episodic and chronic migraine who completed a test treatment with the REN and found there to be only 1 device-related adverse event (AE; 2%) which was a temporary feeling of pain in the arm.⁵ The results showed that pain relief and pain freedom at 2 hours were achieved by 71% (28 of 39 participants) and 35% (14 of 39) of participants, respectively.

Click here for more coverage of AAN 2023.

REFERENCES
1. Tepper S, Rabany L, Cowan R, et al. Significant reduction in migraine days with Remote Electrical Neuromodulation (REN) for migraine prevention: A double-blind randomized sham-controlled clinical trial. Presented at: 2023 AAN Annual Meeting; April 22-27, Boston, Massachusetts. Abstract 010. Advances in Migraine Therapeutics session.
2. Theranica's Nerivio Cleared by FDA for Preventive Treatment of Migraine. Theranica. News Release. Published February 28, 2023. Accessed May 3, 2023. https://www.prnewswire.com/news-releases/theranicas-nerivio-cleared-by-fda-for-preventive-treatment-of-migraine-301757472.html
3. Nerivio receives clearance of expanded indication to cover chronic migraine patients. News release. Theranica Biotherapeutics. October 26, 2020. Accessed May 3, 2023. prnewswire.com/news-releases/nerivio-receives-clearance-of-expanded-indication-to-cover-chronic-migraine-patients-301159445.html
4. FDA Grants Theranica De Novo to Market First Smartphone-controlled Acute Migraine-relief Wearable Device. News release. Theranica. May 28, 2019. Accessed May 3, 2023. www.prnewswire.com/news-releases/fda-grants-theranica-de-novo-to-market-first-smartphone-controlled--acute-migraine-relief-wearable-device-300857281.html
5. FDA approves Theranica’s Nerivio for acute treatment of migraine in adolescents. News release. January 25, 2021. Accessed May 3, 2023. https://www.prnewswire.com/news-releases/fda-approves-theranicas-nerivio-for-acute-treatment-of-migraine-in-adolescents-301213967.html