For the unacquainted, digital therapeutics are “evidence-based therapeutic interventions driven by software to prevent, manage, or treat a disease”. They’re patient-facing software applications that have a proven clinical benefit and regulatory clearance.(1)

What separates DTx from your run-of-the-mill health app is the high standard of clinical validation -often from a randomized controlled trial (RCT)- and approval from regulators, which enables them to make claims and seek reimbursement.

Over the last decade, investment into digital therapeutics has grown exponentially, with 4.5 billion invested in 2021 alone (3). Naturally, with all this excitement we wanted to take a step back and ask the question; are digital drugs going to become a promising new frontier for medicine, or will we one day look back and cringe at the overblown hysteria?

In absence of a crystal ball, we cannot know, however there is mounting evidence that these code-based therapies are more than a passing fad. Just in the last few years alone – and especially during the pandemic- digital therapeutics have found their way into numerous disease states, including diabetes, weight management, insomnia, oncology, ADHD, asthma, and many more.

By IDEA Pharma’s count there are a little over 170 digital therapeutics, either on the market or in development, across various disease states in the US and EU (2). While most are still in development, the FDA has approved approximately 40 digital therapeutics since the first was cleared in 2017 (2).

But what is most impressive, and I would argue the greatest indicator of their potential value, is the fact that both marketed and incoming digital therapeutics are demonstrating meaningful improvements in clinical outcomes for patients that are on par (or in some cases better) than traditional pharmacological agents.

But don’t just take my word for it, below are three examples of digital therapeutics already providing meaningful benefits to patients:

Moovecare, by Sivan uses weekly questionnaires and a clinically validated algorithm, to track treated lung cancer patients for early signs of relapse. This seemingly simple solution demonstrated it provides an improved median overall survival-benefit of 6 months compared to usual care in a Phase III RCT (6). By detecting signs of relapse earlier than traditional practices, patients were able to get on treatment sooner. In a subsequent analysis of the trial, Sivan showed that Moovecare was not only cost-effective but provided costs savings compared to traditional monitoring (7). This robust efficacy and cost-effectiveness data allowed the product to become the first approved and reimbursed DTx in France, opening the doors for additional DTx products. With approval and reimbursement in-hand, Sivan is now focusing on driving awareness and adoption and scaling beyond France.

Big Health is another digital therapeutics developer with two validated products providing meaningful patient benefits. The company developed Sleepio for insomnia and Daylight for anxiety, both offering digital CBT programs validated in RCTs. Sleepio demonstrated that it provides 76% of patients with clinically meaningful improvements in sleep efficiency compared to just 29% and 18% of patients on placebo or usual care, respectively (4). Subsequent analyses showed significant cost savings at the primary care level. The data for these were robust enough to persuade the NHS to strike a deal with the company, providing the therapies to all Scottish residents free of charge. The company is also using this data to make in-roads in the US, recently gaining coverage through CVS Caremark’s pharmacy benefit management business in October 2021 (5).

Unlike the other two, Natural cycles, a DTx leveraging temperature to determine user’s fertility status, took an indirect path to become a DTx. Initially launched as a simple ‘fertility awareness’ health app Natural Cycles started as unvalidated and unapproved app. However, by collecting real world data from app users, the company was able to gather enough data (from over 18,000 users) to publish compelling real-world efficacy as a contraceptive. The data (indirectly) is on par with most contraceptives including hormonal based therapy (8). Through the real-world data, the company was able to gain clearance in the EU and is currently marketed as a digital contraceptive and pregnancy planning tool. Despite this, and significant usage from paying customers, the company has yet to gain acceptance with payors due to a lack of clarity from regulators on reimbursement of digital contraceptives, hindering commercial potential.

Revisiting the question; are digital therapies a promising new frontier for medicine or a passing fad? While we can’t know for sure, I would posit that the clinical data from these three examples (and many others like them) indicate that there is serious value and viability in these digital medicines.

And if you’re not convinced yet, lets also consider some additional advantages of DTx over traditional pharmacological agents:

• Unlike pharmacological interventions, DTx carry little to no side effects

• The intrinsic properties of DTx can be easily and directly ‘edited’ to provide optimized patient outcomes, something that is impossible with molecules and biologics

• DTx can be iterated after launch based on feedback loops or AI guided improvements (something that cannot be done with pharmacological agents beyond formulations)

• DTx can be designed and validated at a (relatively) lower cost

• DTx can be sold for (relatively) lower cost while still providing cost savings

Yet you may ask, with all these positive aspects and proven benefits, why haven’t these novel therapies made their way into the mainstream?

Well, there have been several key challenges to date. Firstly, is the issue of developing a functional commercial model; many companies are still struggling to determine who will actually pay for digital therapeutics (e.g., healthcare system vs. insurance companies vs. individual patients, etc.).

The second, related challenge, is the fact that vague or incomplete policies (especially in the US) have led to limited or no reimbursement from private and government payors.

The third issue is related to the limited awareness of these solutions within healthcare communities, including Physicians who are largely ignorant of the clinical benefits of DTx.

While each of these are very real challenges, I believe they are, with time, surmountable. Based on the clinical data (and not just investment or LinkedIn article numbers) I believe it more likely that we are not just experiencing another fad but rather, are at the beginning of a new frontier of medicine that will open a multitude of new avenues to improve how we treat and manage illnesses with software.

One can envision a world where the data we bring to our doctor provides more insight into our health than our physical body; that every pharmacological prescription comes with a complimentary digital therapy prescription, and where pharmaceutical R&D departments will be comprised of one part lab bench and one part software engineer.

References

1. https://dtxalliance.org/advancing-dtx/

2. IDEA Pharma database on digital health assets

3. https://rockhealth.com/insights/2021-year-end-digitalhealth-funding-seismic-shifts-beneath-the-surface/

4. https://pubmed.ncbi.nlm.nih.gov/22654196/

5. https://www.bighealth.com/news/cvs-health-adds-big-healths-digital-therapeutics-to-point-solutions-management/

6. https://jamanetwork.com/journals/jama/article-abstract/2721170

7. Thibaut L, Basch E, et al. Cost-Effectiveness of Web-Based Patient-Reported Outcome Surveillance in Patients With Lung Cancer. Journal of Thoracic Oncology. 2019. DOI:https://doi.org/10.1016/j.jtho.2019.02.005

8. Berglund Scherwitzl, et al., 2017. Perfect-use and typical-use Pearl Index of a contraceptive mobile app. https://pubmed.ncbi.nlm.nih.gov/28882680/