Updated: 7 days ago
In the first instalment of the Bioelectronics series (What are Bioelectronics and Neuromodulation?), we covered this technology at a fairly high level. This time, we’ll explore what neuromodulation (predominantly device technology) is doing for healthcare today, the major players in the industry, and how it’s regulated.
How is neuromodulation being used?
Neuromodulation refers to any technology that acts directly upon nerves to achieve health benefits. Nerve activity is altered by the introduction of pharmaceutical drugs or electrical stimulation. Chemical methods of neuromodulation, such as the epidural, have been around since the 1920s. Electrical neuromodulation can trace its origins to the introduction of the electronic pacemaker in 1957. Since then, electrical and electromagnetic neuromodulation technology has been adopted in many other healthcare solutions, positively impacting the lives of patients. Previously, patients were required to spend time in inpatient hospitals and specialist neurological centres. Today, due to less invasive procedures and smaller implants, patients of most procedures can be in and out of an outpatient facility within a day. Examples of bioelectronic devices for neuromodulation include:
Spinal Cord Stimulation (SCS) Inspired by Melzack and Wall’s Pain Gate Theory (1965), Spinal Cord Stimulation was developed to treat chronic pain, by blocking pain signals in the spine from reaching the brain.
Deep Brain Stimulation (DBS) In Deep Brain Stimulation, electrodes are inserted into movement centres in the brain, primarily treating motor dysfunctions such as Parkinson’s Disease, Essential Tremor, and Dystonia.
Vagus Nerve Stimulation (VNS) The vagus nerve transmits information between many brain regions and abdominal organs, and therefore neuromodulation of the vagus nerve has many possible therapeutic benefits. Consequently, a variety of issues are treated through VNS, including epilepsy, cardiovascular and respiratory disorders, gastrointestinal diseases, migraines, and depression.
Sacral Nerve Stimulation (SNS) SNS Addresses communication issues between the bladder and/or bowel and the brain to restore normal organ function.
Lesser-known stimulation categories include:
Hypoglossal Nerve Stimulation for sleep apnea Stimulation of the tongue is used whilst the patient is asleep to keep their airways open.
Gastric Electrical Stimulation Here, stimulation of nerves in the stomach helps to move food through the digestive tract, alleviating digestive symptoms in patients with gastroparesis.
Neuromodulation side effects and drawbacks
Advances in surgical techniques over the last half-century have dramatically decreased both the difficulty and the risks of implanting a neuromodulation device.
The side effects and risks of infection are therefore minor, and in line with those of other common surgical implantation procedures. Extensive tests and MRI scans are completed before any surgery to avoid adverse effects where possible, and patients are also given the opportunity to ‘test drive’ some therapies to see for themselves whether the benefits outweigh these minimalised risks. An example of this is SCS, where patients trial the system for a week. The only difference here is that unlike the long-term implant, the temporary trial system has a stimulator device which sits outside the body. The real challenge of neuromodulation is identifying the ideal electrical stimulation settings for each patient. This process is time-consuming and optimisation by the primary care physician or by a specialist implant programmer can take months. Stimulation to the wrong fibres can lead to an unpleasant tingling sensation around area of the implant, though this does at least serve to help in determining correct settings.
These difficulties in identifying optimal stimulation parameters can negatively impact treatment efficacy. However, advancements by BIOS Health have the potential to accelerate this process using neural biomarkers to identify personalised stimulation parameters for each patient. This will maximise treatment efficacy, so patients experience more effective therapy, and receive treatment benefits sooner. Download the whitepaper for more information on our technology.
Who regulates and approves neuromodulation devices in the US and Europe?
As with any device, on occasion, there are product recalls. For the US, regulation of medical devices lies with the Food and Drug Administration, while in Europe the situation is more complex... In Europe, the EMA (European Medicines Agency) is responsible for evaluating the quality, safety and efficacy of marketing authorisation applications assessed through the centralised procedure. In addition, each country has its own regulatory authority who refer back to the EMA when necessary. For example, in the UK, applications for approval and to market a device within the European Union would be made to the MHRA (Medicines & Healthcare products Regulatory Agency); an executive agency, sponsored by the Department of Health and Social Care within the UK government. However, this may change after the UK has left the EU (2).
Players in the neuromodulation market
As shown in the timeline above, Medtronic made an early start with FDA approval in 1989 and has been the market leader ever since, producing neuromodulation devices in almost every category discussed earlier. Other major players include Abbott, Boston Scientific, Nevro, LivaNova and Axionics, each of whom produce devices in one or more neuromodulation categories. But as shown below, new competitors, investors and neurotech hubs are accelerating innovation in this space.
Neuromodulation market challenges
While the regulatory pathway is developing and encouraging for bioelectronics, progress in updating reimbursement models has lagged as payors seek to better understand the range of potential benefits they can deliver (3), including interoperability and the value of data and algorithms. As a result, payors continue to rely upon existing reimbursement models to provide patients swift access to these cutting-edge treatments but these models generally fail to reflect the full range of potential benefits available to patients, clinicians, and healthcare systems.
"A 'Pay-for-Device' reimbursement model limits collaborative engagement between innovators and providers, restricting stakeholders’ ability to deliver ‘state-of-the-art’ healthcare for patients with chronic diseases. Current models result in misaligned incentives and present several key limitations, all stemming from the fact that a pay-for-device reimbursement model does not focus on the value delivered to patients over time, and instead focuses on covering the cost of goods sold. This results in a transactional interaction between innovators and payors, which disincentivises innovation to develop ground-breaking therapies that improve patients’ treatment experience and drive therapeutic benefits." Bioelectronics reimbursement models primer BIOS Health in collaboration with Legal & General
Escalating costs in healthcare (3) mean hospital executives are increasingly having to be savvy in evaluating their medical device assessments and purchase procedures. Even though neuromodulation devices provide patient benefit over several years, they are typically paid for completely upfront at the time of the implant procedure. This is in contrast to drug-based interventions, in which the cost of therapy is spread out over the months or years that a patient is prescribed the drug. Therefore, drug-based interventions have historically been perceived as the cheaper treatment path, even if the lifetime cost of a drug-based therapy is higher, or overall efficacy is lower than a neuromodulation therapy. Furthermore, because drugs can easily be changed or stopped at any time, invasive implant therapies are often considered as the last line of defence treatments if drug-based therapies are unable to manage the disease. New advancements in bioelectronics leveraging AI, mean that other device benefits now need to be considered. For example, the benefits of an AI-powered device would also include interoperability, real-time therapy auto-optimisation, and the value of data and algorithms. Innovative reimbursement models that consider these benefits can be a powerful force to support continuous innovation.
Innovation growth drivers
Thankfully a number of drivers are pushing advancements forward from all directions. In much the same way as decoding the human genome has unlocked a series of advancements in precision medicine (from tailored cancer treatments to covid-19 vaccines), so too is decoding neural signalling unlocking a new wave of targeted therapies. With every new amazing advancement, it’s becoming clear that neural is the next frontier in precision medicine, as neural mapping discoveries are unlocking new possibilities for neuromodulation and/or neural digital therapies.
Rising disease prevalence and market competition
With two billion people across the world expected to be over 60 years old by 2050, the prevalence of neurally mediated diseases is rising (4). These include cardiovascular and respiratory diseases, rheumatoid arthritis, Alzheimer’s and Parkinson’s. The good news here is that new research and the market opportunities arising from this are encouraging new innovators to jump into the neurological pool. With each new indication approved, each treatment success obtained, the more faith insurance companies, investors and health providers will have in neuromodulation technology. – Further increasing the number of competition and technological advances.
Based on market requirements, at the forefront of emerging technology to come, will be closed-loop therapies and multi-indication systems for more holistic treatments. As touched on in the last blog, BIOS Health is bringing a whole new dimension of innovation to the neuromodulation market. By pioneering the technology to read and write neural signals using AI and neural interfaces, BIOS will be providing the technical foundations on which to develop new closed-loop therapies to cover a range of chronic diseases. Neuropace has also made a start with a closed-loop system. Their RNS® system constantly measures brain activity (using EEG signals), then turns on the therapy sensors when an epileptic event is about to occur. Saluda Medical, a relatively new player, also made a splash last year when they gained FDA approval for their closed-loop SCS system. Less invasive, smaller or reversible devices are perhaps an obvious trend, but an important one when it comes to device placement in the body. Advances in device design and surgical techniques over the last half-century have already dramatically decreased side effects, reduced patient recovery times, and allowed for increased patient access to neuromodulation therapies. Companies such as Syncron are pioneering additional breakthroughs in minimally-invasive approaches with their Stentrode™ brain-computer interface, which enables those with severe paralysis to operate computers and communicate with the power of neural signals. Minimally invasive, Stentrode doesn’t even require open surgery as the device is placed in the motor cortex of the brain via the jugular vein.
Economic and unpredictable drivers
Another perhaps unexpected innovation driver has been the global pandemic. In May 2020, the FDA gave emergency approval to Liberate Medical for their VentFree™ Respiratory Muscle Stimulator. Long-term use of ventilators often causes breathing muscles to weaken in patients, binding them to continual use even after the illness has passed. The introduction of the non-invasive VentFree ™ enabled ventilators to be reused where needed in a shorter timeframe.
According to Eroom's Law (first observed in the 1980s) new drugs are taking longer and becoming more expensive to develop over time. In fact, the inflation-adjusted cost of developing a new drug roughly doubles every nine years. This trend is motivating pharma companies and healthcare investors to explore new and novel therapy development areas, leading to increased investment in neuromodulation therapies.
The future of neuromodulation
In summary, neuromodulation is a large and fast-growing market. In 2019 the market value was $3.8 billion but is expected to rise to $6.5 billion by 2025 (5). Large incumbent players have had a head start, and challenges have made it tricky for new players to get onboard. However, emerging technologies are pushing the boundaries of the market, opening significant new possibilities in the treatment of chronic disease. And if new tech is successful enough to render current offerings redundant, new players could quickly steal market share. This is a view shared by many deep tech pioneers including BIOS' CEO Emil Hewage:
“What is certain about the future, is that there are many more issues coming, but Europe has a lot of deep tech technologies incubating. In healthcare, deep tech is really fertile ground for these next-generation solutions.” Emil Hewage CEO, BIOS Hello Tomorrow Conference, Deep Tech Academy Fireside Chat, Paris
Like a stone tumbling down a hill, as more holistic and dynamic treatments are developed, more nervous system mapping understood, more indications will be achieved, and momentum gained. Leading to more faith being given by insurance companies, investors, and providers; spawning further opportunities for new market players and advancements in research and technology.