By Deborah Borfitz

December 11, 2019 | Israeli biomedical technology company Theranica is intent on making its new-to-market remote electrical neuromodulation wearable device a first-line treatment for migraines of every type. As of early December, early adopters of Nerivio included 2,176 patients at nearly 150 headache clinics around the US, increasing at the rate of about 100 users daily, according to Alon Ironi, co-founder and CEO of Theranica.

The US Food and Drug Administration (FDA) authorized Nerivio for marketing in May for the acute treatment of migraines in adults who do not have chronic migraine. In October, Theranica launched a pilot with the headache clinics as a proving ground for the software-controlled device, says Ironi.

Specialized headache clinics are run by leading migraine experts and generally the highest-level resort for patients unable to find pain relief elsewhere, he points out. “If we can convince them of the efficacy and safety of the device then the rest of the journey will be easier.”

Theranica’s mission directly and deliberately challenges the Western medicine norm of treating maladies with either a drug or surgery, says Ironi. “Theranica is trying to demonstrate that this is not the only way to treat certain diseases. Drugs are extremely potent… but not necessarily the best solution for pain, especially idiopathic pain.”

Based on the clinical data collected from Nerivio to date, including a study published in The Journal of Headache and Pain in July, the device is comparably effective to commonly prescribed migraine medications but with fewer side effects, says Ironi. The price is also attractive at $8.25 per migraine, on par with generic drugs and far below other treatment regimens that can run upwards of $75 per dose.

During the limited market launch, Theranica will be using feedback from pilot participants to improve patient education materials and refine the software-controlled device itself, Ironi says.

Nerivio runs off an app on a smartphone, which controls the electrical current that gets painlessly delivered through battery-powered electrodes attached to a patient’s arm—as has been demonstrated on most of the 269 physicians now prescribing it to their patients, Ironi says. “Stimulation is very well perceived, but not painful. A lot of patients would describe it as a comfortable, tingling sensation.”

Patients don’t need to be glued to their phone during the 45-minute treatment, he adds. At the completion of treatment, the device shuts down automatically, “even if you drop your phone into the ocean.”

After 12 uses of Nerivio, users pick up a new device and can mail the old one for recycling to the California Electronic Asset Recovery (CEAR), Ironi says.

Getting the device into clinical use was no small feat, Ironi notes. Market approval of Nerivio required meeting the same clinical efficacy and safety standards as prescription medications, in addition to all the regulatory expectations of medical devices and healthcare software.

Whether to pursue payer reimbursement remains an open question. Many patients and physicians have discouraged Theranica from jumping through the hoops with payers, since Nerivio is affordably priced at $99 for 12 treatments, says Ironi. Payers, meanwhile, have been encouraging Theranica to raise the price closer to $400 or $500 and give them a share of the profits via rebates.

How It Works

Nerivio induces conditioned pain modulation, based on the well-described “pain-inhibits-pain” phenomena discovered in the late 1970s in experiments with mice, says Ironi. It wasn’t until around 2003 that different groups of researchers in the US, Israel and Italy started to investigate the mechanism of action in humans. Nerivio is the first instance of the concept being applied in a therapeutic device, he adds.

Treatments activate the descending mechanism of pain processing rather than inhibiting ascending pain signal transmission, as is done with transcutaneous electrical nerve stimulation (TENS) units, says Ironi. The stimulation provided by Nerivio is “designed to travel to specific locations in the brain stem to trigger this endogenous pain mechanism and… release neurotransmitters throughout the entire body to shut down certain types of pain, and migraine happens to be one of them.”

Although the pain mechanism he describes is native to the human body, it is dysfunctional in migraine patients. Like a perfectly good car that won’t start, they need “another car and a set of jumper cables,” says Ironi, making the analogy with Nerivio.

Unfortunately, migraine is a chronic disease even in patients that experience symptoms episodically, Ironi continues. In the absence of a cure, the quest is to end the pain one migraine attack at a time. Even preventive remedies, such as Botox injections and more recently calcitonin gene-related peptide (CGRP), can at best reduce the frequency of migraines.

A Nerivio prescription typically provides access to between 12 and 24 device refills and, when refills are about to be exhausted, patients are alerted by the smartphone app, Ironi says. Prescription fulfillment, dispensing, and home delivery is currently provided by Quick Care Pharmacy, based in Rancho Cucamonga, California.

Generating Evidence

With Nerivio, the goal is to treat migraine pain at the onset of an attack. In a May 2019 study published in Headache, it was found to achieve pain relief at two hours in 66.7% of patients—comparable to the “very best medications on the market” although not in a head-to-head contest, Ironi says.

The device is currently approved for use in adult patients experiencing migraines with or without aura, and its utility in treating chronic migraines (at least 15 days of migraines a month) is now under study, says Ironi.

Guidelines of the International Headache Society recommend exploring the benefits of new acute treatments in individuals with chronic migraine only after completion of initial efficacy trials with episodic sufferers, he notes. To that end, Theranica recently started a clinical study with about a dozen US-based hospitals specifically targeting chronic migraine patients. Results are expected to be presented in May 2020.

Another study also just started at another 13 clinics around the US to test the efficacy and safety of Nerivio for the treatment of acute migraines in adolescents aged 12 to 18 years old. This is an even bigger area of unmet need, Ironi says, because physicians are much more reluctant to prescribe drugs to adolescents and their parents also have reservations. The indications for use of most migraine drugs are limited to adults.

The study with adolescents is scheduled to end next summer and the data will be submitted to the FDA, says Ironi. Other clinical studies will follow near the end of 2020 and won’t necessarily focus on migraine but several other indications, including post-traumatic headache.

Widescale Availability

Based on early positive feedback and results from the headache clinics, the pilot has been shortened from an initially planned six months to four, says Ironi. The next step is to provide telemedicine access to Nerivio, details of which will be publicly shared at the end of January.

Nerivio has already been gifted with some free publicity by being named one of TIME’s best inventions of 2019, Ironi points out. Calls and emails have been flooding in from physicians and patients seeking access to the device.

Partnerships with a pair of telemedicine companies on the east and west coasts of the US will effectively broaden device availability to migraine patients nationwide, he says. Patients will be able to click a link to be redirected to one of the telemedicine platforms where they can fill out a questionnaire and have an affiliated physician decide if they are an appropriate candidate for Nerivio.

Starting next year, additional specialty pharmacies may be needed to process prescriptions from brick-and-mortar clinics, says Ironi. A soon-to-be-named medical device distributor will also expand product access to urgent care centers, emergency rooms and hospitals.

The market potential is enormous. In the US alone, $3 billion is spent annually on migraine medications, roughly 60% specific to drugs for acute treatment, says Ironi. “After speaking to hundreds of physicians in the American Headache Society, I cannot think of a reason why Nerivio would not be the first-line treatment for everybody with migraine. We’re aiming high… not viewing this device as an esoteric adjunct.”