Nerivio Remote Electrical Neuromodulation Meets Primary End Point in Preventive Migraine Study

Newly announced results from a double-blind, placebo-controlled study (NCT04828707) assessing Nerivio, Theranica’s remote electrical neurostimulation (REN) device, showed that the therapy met its primary end point of statistically significant reduction in monthly migraine days when used as a preventive. The company will continue to work with the FDA on the regulatory process of the therapy as a potential preventive therapy for migraine.¹

In a cohort of 248 patients with at least a 6-month history of headaches, treatment with Nerivio resulted in a reduction of 4.0 migraine days per month from baseline, compared with reductions of 1.3 days in the placebo group (net therapeutic gain, 2.7 days; P <.0001). In terms of impact based on migraine severity, those with chronic migraine experienced a reduction of 4.7 days, compared with 1.6 days for placebo (P = .001) while those with episodic migraine experienced a reduction of 3.2 days, compared with 1.0 days for placebo (P = .003).

"These data demonstrate Nerivio's potential to provide a new nonpharmacological preventive treatment option for people with migraine,” primary investigator Brian Grosberg, MD, director, Hartford Healthcare Headache Program, said in a statement.¹ "The high efficacy of Nerivio compared to placebo, with favorable safety and tolerability, suggests that REN could be a beneficial nonpharmacological therapy option for both preventive and acute treatment of migraine, subject to FDA approval."

Patients included in the study were between 18 to 75 years old, had a history of 6 to 24 headache days per 28-day period for each of the 3 months preceding the study, and were permitted to remain on 1 medication with possible migraine-prophylactic effects. The study excluded those with an active implanted electrical and/or neurostimulator device, uncontrolled epilepsy, a history of use of opioids or barbiturates, or who may be pregnant or breastfeeding. Patients underwent a screening visit, followed by a 4-week baseline phase, an 8-week double-blind preventive treatment phase, and a 4-week open-label phase.

In total, 40% of the 248 study participants used concomitant preventive medications, mainly prescribed oral medications, calcitonin gene-related peptide monoclonal antibody injections, and onabotulinumtoxinA (Botox; Allergan) injections. Findings for this subgroup were similar to the overall population, as treatment with Nerivio resulted in a reduction of 3.5 monthly migraine days compared with 1.5 days for those on placebo (P = .03).

"There is a growing recognition that certain chronic pain diseases, such as migraine, may be treated with therapies other than pharmacological agents, or in combination with those. This is validated by clinical evidence from randomized controlled studies such as this one, as well as real-world evidence studies," Alon Ironi, chief executive officer, Theranica, said in a statement.¹ "It is well-known that individuals with migraine have varied responses to therapies, and sometimes respond best to a combination of different modalities. The results of this study further support the notion that migraine care should develop beyond solely pharmaceuticals, and Theranica is a leader in scientifically exploring and applying this novel non-pharmacologic approach for patients and providers."

Cluster Headache Prevention Clinical Trials Need to Focus on Efficacy, Natural History of Disease

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Nerivio continued to show its superiority over placebo in several other end points, including a reduction of 4.5 headache days per month from baseline, compared with a reduction of 1.8 days in the placebo group (P <.0001). Additionally, Neirivio continued to outperform placebo on moderate/severe headache days (3.8 days vs 2.2 days; P = .005), percentage of patients who experienced a reduction of headache days and moderate/severe headache days, mean reduction of acute-medication days (3.5 days vs 1.4 days; P = .001), and more.

Since it became the first FDA-approved smartphone-controlled prescribed wearable device for the acute treatment of migraine in 2020, there have been several analyses highlighting Nerivio’s benefit across a range of migraine conditions. Recently published post-hoc findings from a trial of patients with chronic migraine showed that Nerivio was similar to standard-of-care medications, suggesting the treatment could be a nonpharmacological alternative for this patient population.²

In that study, among a cohort of 78 adults with chronic migraine, 62.8% (49 of 78) of REN-treated patients demonstrated significant single-treatment pain relief 2 hours after initiating treatment, as opposed to only 48.7% (38 of 78) of those on standard care (P = .056). Additional results showed that 64.1% of the patients achieved constant pain relief with REN, compared with 57.7% of those on standard-care medications (P = .369).