Over the past few years, digital therapeutics have emerged as a new asset class in healthcare. Recently, the digital therapeutics industry has seen significant growth and market traction, as evidenced by multiple FDA approvals, reimbursement from payors, large commercial deals, successful clinical trials, and investment in the area. These developments have enabled the further differentiation of digital therapeutics from other digital health modalities. Digital therapeutics are defined as products that “deliver evidence-based therapeutic interventions to patients that are driven by high quality software programs to prevent, manage, or treat a broad spectrum of physical, mental, and behavioral conditions” (Digital Therapeutics Alliance). As such, these products make stronger claims than other health and wellness technologies about their ability to impact physical and mental health, necessarily making them subject to higher clinical and regulatory standards.
When pioneering a new asset class in healthcare, such as digital therapeutics, it is important to identify how these products work by elucidating delivery methods and mechanisms of action that make these products therapeutics. At MedRhythms, our mechanism of action, auditory-motor entrainment, is delivered through music by our patented software platform. Our digital therapeutics use music as an external auditory stimulus to directly target the motor system and activate the entrainment mechanism of action. While the term mechanism of action has traditionally been associated with the biological interactions through which pharmacological treatments affect the body, the digital therapeutics industry has demonstrated that non-pharmacological treatment modalities can target biological mechanisms to improve outcomes as well. In MedRhythms’ case, our digital therapeutics target neural circuitry to trigger our mechanism of action. Due to neuroplasticity, this can, over time, lead to lasting physiological changes toward clinical outcomes, including improvements in walking speed and reduced fall incidence (Thaut et al., 2018). The mechanism of action is central to all digital therapeutics and is a differentiating feature within the broader digital health landscape. In many ways, digital therapeutics are more similar to prescription pharmaceuticals than they are to other digital health and wellness products.
The qualities that distinguish digital therapeutics from other digital health products have started to be more clearly articulated over the last year in articles such as HealthXL’s “Digital Health, Digital Medicine, Digital Therapeutics (DTx): What’s the difference?” Less discussed are the differences between the various treatment delivery systems that characterize digital therapeutics. Since the early days of the industry, many digital therapeutics have approached improving outcomes by changing patterns of behavior. Companies such as Pear Therapeutics and Click Therapeutics have used variations of behavior change interventions, including cognitive behavioral therapy (CBT), to achieve clinical goals. However, behavior change is not the sole path that digital therapeutics can take to have a meaningful impact on health outcomes.
Companies such as MedRhythms, Akili Interactive, Cognito Therapeutics, Kaia Health, Hinge Health, and Palo Alto Health Sciences, are developing digital therapeutics that directly target neural circuitry and other physiological systems through external sensory stimuli, including music and video games. The distinction between delivery methods does not make one mode superior to the other from a health economic or clinical outcomes standpoint. However, to fully understand digital therapeutics, it’s important to understand the clinical principles, delivery methods, and mechanisms of action employed by the industry leaders.
The direct auditory stimulation that enables MedRhythms’ mechanism of action is delivered through a digital therapeutic system that uses music, sensors, and software (see Figure 1). Rhythmic music is delivered to enable the mechanism of action: auditory-motor entrainment. Specifically, auditory-motor entrainment refers to the coupling of the auditory and motor system to fire in synchrony with each other in response to an external rhythmic cue. The rhythmic stimulus causes the auditory-motor connections that exist in the reticulospinal tract to influence the excitability threshold of motor neurons and prime the motor system (Melville & Rossignol, 1976). The consistent auditory cues of a rhythmic stimulus provide predictable temporal cues that impact firing rates of auditory neurons. This leads motor neurons to fire in synchrony with the auditory neurons, resulting in auditory-motor entrainment. This synchrony happens at a subcortical level and can occur below levels of conscious thought (Thaut et al., 2014). Neuroimaging research has shown that motor training with rhythm can lead to white matter changes in the arcuate fasciculus in healthy populations, demonstrating evidence of neuroplasticity (Moore et al., 2017).
This foundation of neuroscience research led to the development of Rhythmic Auditory Stimulation (RAS), a standardized intervention designed to improve functional walking outcomes in those with neurologic injury and disease. The efficacy of RAS has been demonstrated across a range of disease states, including stroke (Thaut et al., 2014), multiple sclerosis (Conklyn et al., 2010), Parkinson’s disease (Thaut et al., 2019), cerebral palsy (Ghai et al., 2018), and the aging population (Ghai et al., 2017). Beneficial clinical outcomes of RAS include increased symmetry of muscle activation, diminished timing variability (Koshimori et al., 2019), improved velocity, decreased fall risk (Thaut, et al., 2018), and increased stride length (Suh et al., 2013), spatial symmetry, and cadence (Thaut, et al., 2018).
With the help of the team’s clinical expertise and this foundation of research, MedRhythms has developed a patented digital therapeutic platform that is designed to deliver RAS through customized interventions at scale. MedRhythms has an active pipeline of digital therapeutics in development, targeting rehabilitation and prevention across a range of indications in neurologic injury and disease, including Stroke, Multiple Sclerosis, Parkinson’s Disease, and Aging, the most advanced of which is designed to benefit those with post-stroke walking impairments.
“These digital therapeutics, due to their ability to directly stimulate the brain, are most closely analogous to pharmaceuticals that target specific brain regions,” said Brian Harris, co-founder and CEO of MedRhythms. “Moreover, because of their clinical efficacy, digital therapeutics have the potential to fill in treatment gaps where there aren’t solutions, to be used in combination with existing pharmacological interventions, and to serve as alternatives to certain drugs.”
While digital therapeutics companies are navigating regulatory and reimbursement pathways, many have already demonstrated the therapeutic benefits of these products and their potential for addressing unmet needs in the larger healthcare industry. We can expect more digital therapeutics to be developed across behavior change and sensory stimulation modes of delivery in the coming years. Both the advancement of technologies that directly target neural circuitry with external sensory stimuli and the growth of populations suffering from unmet medical needs will, together, encourage the expansion of the digital therapeutics market.