What is Nerivio?

The pilot study was a single-center, prospective, double-blind, randomized, crossover, sham-controlled pilot study aimed to assess the safety and efficacy of non-invasive remote electrical neuromodulation (REN) with the Nerivio device for the acute treatment of migraine. In this study, 86 people with migraine with or without aura (in accordance with International Classification of Headache Disorders [ICHD] classification criteria) who had 2–8 attacks per month without preventive medications for at least 2 months were recruited. The participants were requested to treat migraine episodes at home using the device, which randomly provided one of four different stimuli programs differentiating in pulse width and one sham stimulus. Pain levels were self-reported via a smartphone application at stimulation onset and again at 10, 20, and 120 minutes after stimulation onset. The primary endpoint was the proportion of participants reporting pain decrease of at least 50% at 2 hours post-treatment in at least 50% of completed treatments. The analysis of the primary endpoint was performed on 71 participants who successfully treated at least one migraine attack and have not used rescue medications concurrently with REN treatments. This analysis revealed a 64% rate of at least 50% pain reduction at 2 hours post-treatment, in at least 50% of completed active treatments. This rate was significantly higher than the 26% rate found for the sham treatment (p=0.005). In this study, no device-related adverse events and no side effects were reported.

The pilot study (TCH-005) was prospective, open-label, single arm, dual-center study aimed to demonstrate the safety and efficacy of Nerivio remote electrical neuromodulation device for the acute treatment of migraine with or without aura in patients with chronic migraine (>15 headache days/month). This study was conducted from September 2019 to February 2020 at 2 sites (USA -1, Israel – 1).

42 participants were enrolled, and 38 participants were evaluable for analyses. A total of 210 evaluable treatments (excluding the training treatment) of qualifying migraine headaches were conducted by the 38 participants included in the analyses, with an average of 5.5±2.6 evaluable treatments per patient per 4 weeks.

The primary, secondary and exploratory endpoints of a single attack were conducted on the test treatment of the final analysis set of 38 participants. Pain relief and pain-free at 2 hours were achieved by 50.0% (19/38; CI95% 33.4-66.6%) and 26.3% (10/38; CI95% 13.4-43.1%) participants, respectively. Pain relief was sustained for 24 hours in 83.3% (10/12; CI95% 51.6-97.9%) of the participants who achieved relief at 2 hours (7 participants did not report pain level at 24 hours and were thus, excluded from the analysis). Nausea, photophobia, and phonophobia disappeared at 2 hours in 58.8% (10/17; CI95% 32.9-81.6%), 37.5% (9/24; CI95% 18.8-59.4%), and 50.0% (8/16; CI95% 24.7-75.3%) participants, respectively. Furthermore, 46.7% (14/30; CI95% 28.3-65.7%) participants experienced improvement in functional ability at 2 hours and 72.7% (16/22; CI95% 49.8-89.3%) participants experienced improvement in functional ability at 24 hours (8 participants with missing data at 24 hours were excluded from the analysis).

Consistency analyses across all attacks (excluding the training treatment) demonstrated that 73.7% (28/38) of the participants experienced pain relief in at least 50% of their treated attacks. Mean pain relief rate across subjects was 58.8%, median pain relief rate across subjects was 60% and the inter quartiles rang (IQR) was 43.67 – 87.50%.

According to the safety analyses, the percentage of participants experiencing at least one adverse event was 4.7% (2/42) with 95% confidence interval of (0.6 – 16.2%). A single device-related adverse event was reported (2.3% [1/4])). The device-related adverse event was moderate, resolved within 48 hours following drug therapy (triptan). There were no serious adverse device-related events and none of the participants withdrew from the study due to adverse events.

The findings of the study demonstrated that Nerivio is effective for the acute treatment of migraine in people with chronic migraine. Acute treatment of migraine headaches resulted in clinically meaningful benefits. Pain relief and pain-free rates were generally similar to those found in people with non-chronic migraine as reported in the Nerivio pivotal clinical study TCH003. Overall, the data reveal consistent response rates from treatment to treatment, with no evidence of reduction in therapeutic benefits over time. Specifically, over 73% of the patients achieved pain relief at 2 hours in more than half of their attacks. The findings of this study also show that the device is safe and well-tolerated. No safety issues were associated with the more frequent use of the device in patients with chronic migraine.

Main study with chronic migraine patients

The pilot study (TCH-006) was prospective, open-label, single arm, multi-center study aimed to demonstrate the safety and efficacy of Nerivio remote electrical neuromodulation device for the acute treatment of migraine with or without aura in patients with chronic migraine (>15 headache days/month). This study was conducted from November 2019 to June 2020 at 9 sites in the USA.

Participants entered a 4-week “Run-in” phase in which they had to report their migraine attacks and continue with their usual treatment care. Participants who reported at least 6 qualifying migraine headaches with pain data at baseline and 2 hours post-treatment were eligible to continue to the “Treatment” phase

Run-in phase

A total of 997 qualifying migraine attacks were reported during the run-in phase by the 126 enrolled patients, with an average of 7.9 attacks per participant. Of these, pain level at baseline was reported on 993 reported attacks.

Treatment phase

A total of 493 evaluable treatments (excluding the training treatment) of qualifying migraine headaches were conducted by the 91 participants included in the analyses, with an average of 5.4±2.8 evaluable treatments per patient per 4 weeks. Medication at 2 hours was used in 54 of the 493 treatments (89.0% compliance rate). Use of medication was considered a treatment failure.

The primary, secondary and exploratory endpoints of a single attack were conducted on the test treatment of the final analysis set of 91 participants. Pain relief and pain-free at 2 hours were achieved by 59.3% (54/91; CI95% 48.5-69.5%) and 20.9% (19/91; CI95% 13.0-30.6%) of the participants, respectively. Pain relief was sustained for 24 hours in 73.3% (33/45; CI95% 58.0-85.3%) of the participants (9 participants did not report pain level at 24 hours and were thus excluded from the analysis). Nausea, photophobia, and phonophobia disappeared at 2 hours in 48.8% (20/41; CI95% 32.8-64.8%), 40.5% (30/74; CI95% 29.2-52.5%), and 44.6% (29/65; CI95% 32.2-57.4%) participants, respectively. Furthermore, 59.4% (19/32; CI95% 40.6-76.3%) of the participants experienced improvement in functional ability at 2 hours (participants with missing data at baseline or at 2 hours were excluded from the analysis) and 50.0% (7/14; CI95% 23.0-76.9%) of the participants experienced improvement in functional ability at 24 hours (participants with missing data at baseline or at 24 hours were excluded from the analysis).

Consistency analyses across all attacks (excluding the training treatment) demonstrated that 57.1% (52/91; CI95% 46.3-67.4%) of the participants experienced pain relief in at least 50% of their treated attacks. Mean pain relief rate across subjects was 50.4%, and median pain relief rate across subjects was 50%. Pain relief in at least 2 of 3 consecutive treatments (first 3 treatments excluding the training treatment) was reported by 64.4% (47/73; CI95% 52.3-75.3%) of the participants.

The percentage of participants experiencing at least one adverse event was 9.1% (9/99) with 95% confidence interval of (4.2 – 16.6%). One device-related adverse event was reported (1.0% [1/99]) in which pain in the arm was felt following the use of the device on that arm. The device-related adverse event was mild, resolved within 24 hours without medication. The other adverse events which were deemed unrelated to the device.

The findings of the study show that Nerivio is effective for the acute treatment of migraine in people with chronic migraine. Acute treatment of migraine headaches resulted in clinically meaningful benefits. Pain relief and pain-free rates were generally similar to those found in people with non-chronic migraine, indicating that Nerivio provides an alternative acute migraine treatment independent of the frequency and severity of migraine headaches.

The results of the study show that Nerivio is safe to use and is well-tolerated. The incidences of device-related adverse events were low with no device-related serious adverse events. The rate of all device-related adverse events was below 2%, which compares favorably to the reported rates for current pharmacological treatments.