Meet the start-up: Theranica's innovation for pain disorders

Alon Ironi, CEO and co-founder of Theranica, spoke to Med-Tech Innovation News about the company’s offering in digital therapeutics, the technology itself and how it all started. 

Tell us about your company. When did you establish yourself and what do you offer?

We are Theranica, a company established in 2016 composed of experienced and ambitious individuals, set on advancing digital therapeutics for idiopathic pain disorders, beginning with migraine. 

Combining innovative neuromodulation therapy with wireless technology, we developed our flagship product Nerivio, a smartphone-controlled wearable therapeutic electroceutical device that harnesses the body’s endogenous pain regulation mechanism to address migraine pain. Nerivio, which is FDA-cleared for the acute treatment of both episodic and chronic migraine, is a drug-free alternative to traditional migraine treatments.

Beyond migraine, additional idiopathic pain disorder can benefit from Remote Electrical Neuromodulation (REN) – including fibromyalgia, back pain, post-surgical pain, and TMJ, to name a few. Having unlocked one of the underlying mechanisms of pain dysregulation, in the future, we can expand our attention to those living with other pain conditions and bring the relief we’ve successfully brought to migraine sufferers to others around the world.

Where did the idea for your start-up come from?

When my daughter was finally diagnosed with migraine after suffering for almost a decade, I saw first-hand how debilitating this disorder could be. The treatments available at the time were exclusively pharmaceutical, many of which were ineffective for her and accompanied by unpleasant side effects. With my high-tech and engineering background, along with my experience as the CEO and co-founder of Siano Mobile Silicon, I began my foray into the field of migraine to try to understand why a disease so prevalent was not receiving the attention it deserved.

Along the way, I was introduced to Professor David Yarnitsky, the head of the Neurology Department at the Technion and head of Neurology at Rambam Hospital in Haifa, who had dedicated his professional life to understanding how pain is regulated in the body. 

Together with Dr. Shimon Eckhouse, Ronen Jashek and Rostislav Barabech, Theranica was born to address this disorder through the lens of modern technology and innovation. We began by investigating the migraine treatment space and identified the need for a drug-free, non-invasive and low side-effect solution that would be affordable for patients. With Dr. Yarnitsky’s research and guidance we developed Nerivio, a smartphone-controlled REN wearable for acute migraine treatment. 

What difference do you think you can make in your particular sector? 

Migraine is the third most prevalent disorder in the world, affecting roughly 1 billion people globally. Migraine and headache pain are leading causes of outpatient and emergency department visits, and remain a critical public health problem, particularly among women during their reproductive years, who are disproportionately affected by migraine.

Migraine is traditionally treated with over-the-counter pain relievers (OTCs), or strong prescription medication. OTCs are often less effective than prescription medication and are usually insufficient for severe migraine cases. Prescription medications can be expensive with minimal insurance coverage and cause harmful side effects, such as medication overuse headaches. Recent innovations have helped introduce wearable devices to the market, but these are bulky devices worn on the head or neck, and often less effective than prescription drugs. None of these options are ideal solutions for someone living with chronic pain.

Nerivio is unique among migraine therapies as it provides a totally non-pharmacological, non-invasive, safe and effective alternative to medication. Nerivio is a therapeutic wearable device placed on the upper arm, which uses REN technology to alleviate pain by stimulating the brain’s endogenous pain inhibition mechanism known as Conditioned Pain Modulation (CPM). It is clinically proven, based on numerous clinical studies and six peer-reviewed scientific publications, showing that Nerivio is non-inferior to prescribed medications in the market. The Nerivio app allows the user to personalise each treatment depending on the intensity of the pain and enables easy tracking of migraine triggers through the user-friendly migraine diary. 

Nerivio was granted FDA authorisation in 2019, and CE mark in 2020 and will be rolled out in Europe in 2021.

Nerivio is already making an impact, used by more than 14,000 patients in 2020 alone, and growing rapidly.

Tell us more about the technology at the centre of your product and service?

Nerivio harnesses the body’s own pain inhibition mechanism, the CPM response, by using REN. This ‘pain inhibits pain’ mechanism, in which a strong, yet non-painful stimulus moderates pain in other regions of the body has been well-documented to be a reliable mechanism for pain reduction.

Nerivio stimulates specific nociceptors on the upper arm above their depolarisation thresholds but below the perceived pain threshold. The noxious information reaches the brainstem and activates the pain inhibitory pathway by releasing serotonin and noradrenalin, which inhibit incoming messages of pain in the trigeminal cervical complex that occur during a headache of a migraine attack.

We originally conducted both a pilot and pivotal study that together demonstrated the safety and efficacy of using remote non-painful electrical upper arm skin stimulation in reducing migraine pain, and the safety of a REN device for acute treatment of migraine. Since then, we have conducted many more studies, including in chronic and adolescent migraine patients that showed the benefits of using REN in these patient populations. 

Who have you had to work with to establish your product and service? 

To develop Nerivio, we worked with many prominent researchers on studies that support the efficacy and safety of Nerivio, including researchers from Harvard Medical School, Mayo Clinic, Hartford Healthcare, and Jefferson University Hospitals.

Nerivio is a prescription wearable, which means patients must take an active first step and visit their neurologist or physicians before using the device. Understanding this was a barrier for some patients, we decided to partner with telemedicine providers such as Cove and UpScript to help broaden the availability of Nerivio to patients across the US. 

In addition, we partnered with California Electronic Asset Recovery, Inc. (CEAR) to recycle Nerivio after the user has completed 12 treatments. It is important to us to bring pain relief to as many people as possible, while inflicting minimum harm on the environment. We believe in the importance of sustainable technology and chose environmentally friendly materials when designing Nerivio. 

Anything else you’d like to add? 

Having worked in this space for about five years now, I am continuously astounded that while migraine is so common, there are many types of migraine that have yet to receive customised, tailored therapies. These patients have gone underserviced for far too long, trying multiple medications only to end up back in bed with the blinds drawn. We want to ensure that people living with all types of migraine can find a non-pharmacological alternative that fits their lifestyle.

Based on the research we have conducted and our understanding of pain in the body, there are many more idiopathic pain disorders that could benefit from REN therapy. While this is a demanding undertaking, we plan to continue clinical development and move beyond migraine to bring relief to people suffering from many different conditions.