Simply Stimulating: Examining the Neurostimulation Sector

To the casual observer, Drew Robinson seemed to be living a charmed life.

He was playing professional baseball—a lifelong dream, boasted an impressive repertoire, had supportive family members and friends, and was earning decent money.

At 27, Robinson appeared to have everything he had ever wanted.

Well, almost everything.

“I was a professional baseball player, had a supportive family, had lived comfortably, but internally, I was still battling a severe level of depression,” the former infielder/outfielder said in an online video. “My negative feelings were a constant weight that I felt at all times, even when I wasn’t aware of them. One of the main things it took away from me was just this overall appreciation for where I was at in life. My depression made it harder to function as a professional athlete, mainly because I always had this other…thing taking away from my focus. When I was playing, I was constantly walking on eggshells, afraid of doing the wrong thing, living with this weight of depression, living with this fear of failing.”

That fear and weight eventually became unbearable. Robinson’s self-doubt, melancholia, and misery intensified as he bounced between minor and major league rosters for the Texas Rangers and St. Louis Cardinals. By the time COVID-19 shut down the world in March 2020, Robinson was drowning in the depths of despair.

He had reached the point of no return.

It was time for the pain to end. The second-guessing, the self-loathing, the constant worrying—Robinson wanted it all gone. For good.

And he knew of only one way to do that: He would take his own life.

On April 16, 2020, at roughly 8 p.m., Robinson sat on his living room couch, pressed a handgun against his right temple, and pulled the trigger. Upon entering Robinson’s head, the bullet almost immediately ruptured his right eyeball, sailed across the orbital wall and through the ethmoid sinuses, fractured his frontal sinus, then whistled past his left orbital floor and exited through his left cheekbone, narrowly missing his other eye, ESPN reported. Somehow, the slug cleared the sinus’ major arteries, sparing Robinson from catastrophic bleeding.

Despite leaving a gaping 1-inch by 1.25-inch hole in Robinson’s head, the self-inflicted gunshot did not meet its objective. The fourth-round draft pick survived his suicide attempt, and despite heavy bleeding, spent nearly 20 hours rambling around his house before dialing 9-1-1 (he reportedly showered, brushed his teeth, took Tylenol for the pain, and scrolled through cell phone text messages).

Robinson underwent four surgeries to repair the physical damage to his face (he now sports a titanium eye socket and prosthetic eye), but the wounds to his psyche were much more difficult to fix. He tried anti-depressants and mood stabilizers (as well as a combination of both), but the regimens failed to lift his spirits.

Yet all hope was not lost. Robinson’s psychiatrist suggested he try a non-invasive, non-drug brain stimulation treatment developed by Malvern, Pa.-based Neuronetics Inc. The company’s NeuroStar Advanced Therapy System uses transcranial magnetic stimulation (TMS) to stimulate the specific brain neurons controlling mood. Clinicians have performed more than 5.3 million NeuroStar treatment sessions in over 147,000 patients, according to the company. NeuroStar is cleared by the U.S. Food and Drug Administration for adults with major depressive disorder (MDD), as an adjunct for adults with obsessive-compulsive disorder, and to decrease anxiety symptoms in adult patients with MDD that may exhibit comorbid anxiety symptoms (anxious depression).

“I realized after going for [several] treatments that it was really easy, really comfortable, and something that I actually looked forward to doing each day,” said Robinson, now a mental health advocate for the San Francisco Giants. “After three weeks I think is when I really noticed a difference in my energy levels, which inevitably allowed me to reframe some of these negative thoughts, which led to a more overall positive outlook on life. Now that I’ve finished with my treatments, I feel so much better, I feel so much more energized, and I feel like I have this huge weight lifted off my chest. I have more clarity now and I feel like I’m able to focus more on the good things, which allows me to not get so tripped up on all the negative little things that can add up throughout the day. I feel like I have a new purpose in life…”

Robinson’s new purpose was born amid a confluence of forces: part luck, part fate(?), and part ingenuity in neurostimulation technology. The market for such innovation is growing as the world’s population ages and the prevalence of neurological disorders and lifestyle-related conditions increases. Grand View Research estimates the sector’s (global) value at $4.5 billion and expects it to swell 12.8% through 2030.

Neurostimulation devices help treat neurological disorders, providing electrical stimulation to intended parts of a patient’s brain, peripheral nervous system, and spinal cord. They are particularly used to treat various conditions such as epilepsy, movement disorders, Parkinson’s disease, chronic pain, and depression.

To better understand the market forces driving innovation in the neurostimulation sector, MPO spoke to several industry experts over the last few weeks. They included:

• Dr. Allen W. Burton, divisional vice president and chief medical officer, Neuromodulation, Abbott
• Rafael Carbunaru, vice president, Research & Development, Neuromodulation, Boston Scientific
• Eric Goorno, CEO, EndoStim Inc. The Santa Ana, Calif.-based medical device firm is developing and commercializing a first-in-class neurostimulation treatment system for drug refractory gastroesophageal reflux disease (GERD).

Michael Barbella: What are the dominant market forces at play in your niche of the neurostimulation sector? What factors are driving these forces and how have they changed in the last five years?

Dr. Allen W. Burton: For us, the prevalence of chronic and intractable chronic pain is the biggest factor in our drive to develop more effective tools to manage that pain. Studies have shown that in the U.S. alone, more than 50 million people suffer from chronic pain. The U.S. Pain Foundation has found that chronic pain is the leading cause of people going to the doctor and costs the nation approximately $635 billion each year in healthcare, disability, and lost productivity costs. At Abbott, our ultimate goal is to deliver products and solutions to simplify healthcare, improve clinical outcomes and provide people suffering from chronic pain with the best treatment experience possible.

Eric Goorno: EndoStim is not on the U.S. market yet, we have been in the market internationally previously. Right now, we are in the middle of the regulatory approval process in the United States and we expect to be the first to market with a neurostimulation solution for GERD (gastroesophageal reflux disease). Other players out there include a full surgical solution, but nobody has a treatment like ours. The first line of treatment for GERD is drugs—typically proton pump inhibitors (PPI)—which can help reduce stomach acid but do not actually cure the disease. There are about 20 million people on PPIs. When PPIs don’t work, there are surgical solutions available, but they are associated with a lot of side effects. The standard of care is an invasive surgical procedure called Nissen Fundoplication. There is also technology from J&J called LINX, it’s a small magnetic ring that is put around the esophagus and there is an endoscopic solution from EndoGastric Solutions. Our technology is less invasive than surgery, has shown high levels of efficacy, and low levels of adverse events. We believe we have an advantage in this area.

Over the past few years, there have been changes in guidance from gastroenterological societies about patient treatment patterns. The guidance is leaning to more readily refer patients for GERD therapy. Once a patient fails two drug regimens, they should be diagnosed to determine whether they have drug-refractory GERD. At that point the recommendation is to consider one of these surgical solutions. So, solutions like ours are becoming more accepted by these societies. In the past, clinicians often kept patients on multiple drug regimens longer than they should have, but the approach is changing. Societies are becoming more willing to adopt these technologies earlier to treat drug-refractory GERD.

Barbella: What kinds of specific neurostimulation applications are exhibiting the fastest growth (pain management, depression, Parkinson’s, other)? Why are these applications growing more than others?

Burton: There is really no one field where development is accelerating over the others. Our goal is to unlock solutions to help treat chronic disease states and we are continuing to investigate different indications in which neurostimulation has the potential to be utilized. Our neurostimulation therapies allow people living with chronic pain and movement disorders to move easier and achieve a better quality of life. Currently, our portfolio of therapies provides a medication-free technology to help chronic pain patients manage their condition and combat the symptoms of movement disorders for those living with Parkinson’s disease or essential tremor.

Goorno: The cardiac market is more mature, so newer markets  for neurostimulation represent new possibilities for companies. [Neurostimulation] is a potentially very lucrative field where you can build a multimillion-dollar company using this technology applied to other large disease states, such as pain management and Parkinson’s.

Barbella: How are machine learning and artificial intelligence impacting neurostimulation technology, if at all?

Burton: For us, there is the potential to integrate AI and machine learning with our NeuroSphere Digital Care tool, which is our connected care management platform that joins proven neuromodulation therapies with powerful digital health tools. One such tool is NeuroSphere Virtual Clinic, which gives people the flexibility and comfort of receiving care anywhere* by connecting with their doctor via secure in-app video chat and an integrated remote programming feature.

Also part of the portfolio is NeuroSphere myPath, which is specifically designed to track and report on perceived pain relief and general well-being to help doctors more closely track their patients as they trial Abbott neurostimulation devices to address their chronic pain. AI and machine learning might one day be able to assist in setting the appropriate neurostimulation dosing based on patient data gathered by their device or doctor.

* Anywhere with a cellular or Wi-Fi connection and sufficiently charged patient controller.

Rafael Carbunaru: Boston Scientific and IBM Research are working to transform the future of chronic pain care. For nearly six years, our organizations have collaborated to better support people living with chronic pain by combining our leading expertise in medical devices, clinical research, information technology and artificial intelligence. By joining forces, Boston Scientific and IBM have developed a novel holistic approach to measure how chronic pain impacts each patient—all with the ultimate goal to allow people living with chronic pain to live their healthiest life. Our work together builds on our vision to create and deploy transformative technologies that help enable more personalized treatment. We are building algorithms and platforms that allow to collect a number of non-invasive metrics from consenting people living with chronic pain, such as mood, movements, pain and sleep into an overarching AI driven platform that can describe the changing state of chronic pain patients. This information is intended to help clinicians gain a more holistic and accurate picture of the state of people living with chronic pain, and with that help them better manage and care for their patients.

While our current work is focused on spinal cord stimulation devices, this work has tremendous potential to be applicable to the entire pain management spectrum….and one might consider the potential to help treat other chronic conditions as well.

Goorno: Our algorithm is pretty straightforward so there is not an immediate use for AI or machine learning, but I think these innovations could be appropriate to optimize or modify our algorithm at some point going forward. One interesting breakthrough is the EVOKE Spinal Cord Stimulation System (Saluda Medical), which features closed-loop stimulation technology that can continually detect neurologocal signals and optimize therapy accordingly. Continuous learning in this closed loop system is a big innovation in this field. Other innovations like smaller battery sizes and rechargeable batteries are becoming a more important part of the market. Rechargeable IPG (implantable pulse generator) batteries are becoming a more preferred option because a battery replacement is not necessary. Replacing a battery requires an additional procedure; you can avoid that if you can recharge the battery.

Barbella:  What kinds of innovations in the neurostimulation space are showing the most promise?

Burton: In May of 2022, we received breakthrough device designation from the U.S. Food and Drug Administration to investigate the use of our deep brain stimulation (DBS) system in treatment-resistant depression (TRD), a form of major depressive disorder (MDD). While Abbott’s DBS system has traditionally been used to help control symptoms for people with movement disorders, evidence suggests that implanting electrodes in the part of the brain that regulates mood could help reduce symptoms of TRD.

For patients who suffer from TRD, deep brain stimulation has the potential to modulate depressive symptoms. Currently, physicians have access to a range of treatments for MDD, also called clinical depression, yet up to a third of individuals diagnosed with MDD do not respond to treatment—even after trying four different antidepressant regimen approaches—resulting in TRD, or difficult-to-treat depression.

Barbella: Has COVID-19 had an impact on product development? If so, how?

Burton: COVID-19 didn’t impact our product development. On the contrary, we were well positioned to meet the COVID-19 challenges and help people continue to get the care they needed because of decisions we made well before the pandemic began.

We made significant investments over the past decade to advance digital and remote health options with the goal of better connecting doctors and their patients across all therapies, including neuromodulation devices.

This investment resulted in the development of NeuroSphere Virtual Clinic, the first neuromodulation app in the U.S. that allows for a true virtual care experience by helping patients interact with their care team from the comfort of their home.

NeuroSphere Virtual Clinic launched in the middle of the pandemic when people were still finding it difficult to get in to see their doctor.

Barbella: What regulatory challenges are impacting the neurostimulation sector, and how are they impacting the industry?

Goorno: For our segment—and I think it’s the case for most if not all neurostimulation technologies—is that we were required to perform a randomized, double-blind, sham-controlled study, the most rigorous type of clinical trial. This was an FDA rquirement because we can put our implant in to all patients, and the treatment arm of the study turns the neurostimulation on while the sham control arm does not turn neurostimation on. Right now, we’re in the process of pulling all the clinical study information and documentation for the regulatory submission itself. We’re looking at a possible FDA approval next year.

Barbella: Please discuss the challenges your company has overcome in developing neurostimulation technology and how it has overcome those challenges.

Burton: One challenge we’ve faced as we’ve begun developing newer technology in neurostimulation is ensuring patients and physicians are educated about the safety and effectiveness of neuromodulation therapies and debunking any misconceptions. While patients are more familiar with pain medications, and healthcare providers acknowledge them as the standard of care to broadly treat pain, there is growing concern and public scrutiny regarding the use of prescription pain medications. Applying direct stimulation may sound intimidating, but patients who use Abbott stimulation devices say they wish they had known about or talked to their doctor about this treatment option sooner.

Patients throughout the U.S. often face difficulties receiving the care they need. Some states only have one provider for the entire area specializing in neurostimulation therapy. At Abbott, we are determined to help patients receive the care they need, when they need it, no matter their location through the advent of our virtual care technology.

Goorno: The barriers were definitely significant. Since we were first of its kind in the market, we had to prove the science, then prove the product’s safety to stimulation parameters,  confirm patient comfort and optimize the treatment for efficacy. It’s a long process and it was especially challenging because we had to develop the algorithm, which is different than let’s say a stent or a device that heals a fracture. There’s a lot more that goes into the science. The controlled, double-blind control study was challenging as well. Developing a first-of-its-kind device is difficult because there are multiple hurdles you have to clear. We recently received Breakthrough Device Designation from the FDA, which was a nice accelerator, if you will. The Breakthrough designation was also a nice confirmation of the uniqueness of our device, the concerning nature of GERD and it substantiated the need for a better solution in the marketplace.

Barbella: How will the neurostimulation market evolve over the next five years?

Burton: As discussed previously, we see the neurostimulation market evolving in tandem with the needs of our patients. As long as people are living with the often-debilitating symptoms of their chronic disease states, Abbott will continue to expand on the research and development needed to allow people to live their fullest lives. This means exploring our technology beyond current indications and providing more treatment options for people who can benefit from neurostimulation.

Goorno: When you’re in the market with these large disease states, a neurostimulation device can be a very attractive solution. Specific algorithms and closed loop feedback are promising innovations for the market. People are going to have to look for nuances in their solutions for this market, whether it be a rechargeable battery, patient-customized treatment, new leadless technology or some other improvement; they will have to find niches that other players have not already found. It’s hard to compete with the big guys like Medtronic and Boston Scientific—you have to look for a differentiator if you are going to go into existing markets. To get through [product] concept to commercialization, a company is going to have to overcome a lot of challenges. You may need $100 million to get a neurostimulation  product from concept to commercialization, so you have to have the funding, the technology, a market need, a sizable patient base, and the know-how to go after something new. We are excited about our prospects, we’re excited to get our technology on the market and start improving the lives of patients with GERD.