Comparing Digital Therapeutics (DTx) to Traditional Pharma

Bernhard Kappe
Bernhard Kappe

This blog contains Chapter 4 of the Orthogonal eBook titled:  Digital Therapeutics (DTx): Accelerating Success Using Fast Feedback Loops. The following are links to each chapter of this eBook:

Although the goal of improving health outcomes is often the same, DTx may differ from traditional pharmaceutical products in several key aspects.

DTx can be brought to market more rapidly than pharmaceuticals

On average, it takes over 10 years to obtain FDA approval for a drug, excluding the initial stages of the drug discovery process.[1] Over a series of clinical trial phases, researchers seeking regulatory approval for a given pharmaceutical must prove that it is effective, safe, and well-tolerated, with an excellent pharmacokinetic profile and no adverse effects. The process to bring novel pharmaceuticals to market in the U.S. and other countries around the world is slow and costly.

In contrast, DTx offers a shorter time-to-market because software-based Tx may require less R&D effort and carry fewer risks than biology- and chemistry-based Tx. DTx are often focused on facilitating behavioral changes that generally entail lower risks to the patient than introducing mass-manufactured chemical and biological substances into the human body. (That said, DTx still need to demonstrate efficacy because there can be a significant negative health outcome for a patient with a significant health condition who chooses an ineffective, newer DTx over an existing Tx such as a prescription drug that is proven to be effective.)

Additionally, DTx may use a previously approved platform for multiple indications, further reducing time-to-market. Akili is working to demonstrate that its platform which is first being used to treat attention control is actually not disease specific and can be adapted to many other types of treatment.

In 2021, Akili Interactive exemplified this DTx advantage by leveraging its FDA-approved Akili SSMETM core technology originally approved for ADHD (see Section 3: Akili Case Study #3 for more details) to enable a treatment for COVID brain fog.

COVID brain fog was first identified in a study published in Neuropsychopharmacology that found difficulties in attention, multitasking, and processing speed were common in hospitalized patients recovering from COVID-19.[2]  Weill Cornell Medicine/New York-Presbyterian Hospital and Vanderbilt University Medical Center are each running randomized control trials that started in May 2021 to evaluate whether the Akili platform (AKL-T01) can help improve cognition in COVID survivors.[3]

Whether addressing public health crises or trying to reduce development time and costs for business reasons, the fast feedback loops of software development, e.g., releasing a beta version of a software-based therapeutic to gain user insights and refine the product offering over a period of several months, may result in faster software product development cycles and faster arrival on the market. Software development can move so quickly that clinical trials may take longer to complete than initial development. Orthogonal’s eBook on Agile in an FDA Regulated Environment outlines how health technology companies can retain Agile principles and remain adherent to FDA guidelines.

DTx can be brought to market less expensively than pharmaceuticals

According to McKinsey & Company, the process of bringing a drug to market can cost a drug company billions of dollars over the course of a decade for the average discovery-to-market cycle, with an average cost of $2.6 billion.[4] A significant portion of this money is spent on demonstrating that the benefits of the drug outweigh its risks. Conversely, the cost of studies to prove the safety and efficacy of DTx can be minimized using iteration and data-driven methods described above. Additionally, because DTx don’t interact biologically with a patient or user, they carry a lower risk of adverse side effects.  These fundamental differences in development processes can reduce total costs and speed up a DTx’s time to market. (On the flip side, the lower investment costs and faster lifecycle of DTx software development relative to pharmaceuticals based on biology and chemistry also greatly reduces the barriers to entry for firms that want to compete with rival DTx offerings.)

In addition, DTx distribution costs could be significantly less than that of a typical drug prescribed in pharmacies, which is approximately 41 cents on each dollar.[5] There is a quantifiable difference between the complexity of publishing an app to an app store for user download and manufacturing, distributing, tracking, and delivering pharmaceuticals across a global supply chain.

DTx has disruptive potential to re-level the pharmaceutical industry playing field that has been shifting towards massive global firms. These global firms are often the only ones in MedTech with the resources and scale to undertake multi-decade, multi-billion-dollar bets on new drugs, with the ability to wait out that timeframe to achieve far more massive financial returns. Such a shift may have profound repercussions for the entire healthcare industry and society at large, including potentially creating new pathways to reduce health disparities that were laid bare by the COVID-19 pandemic.

Unlike pharmaceuticals, DTx can have a service component

Pharmaceutical companies develop and sell a drug, and that is often the extent of their interaction with patients who use those drugs. In contrast, DTx are frequently offered as part of a broader treatment plan that requires ongoing interactions with patients and providers.

DTx companies, such as Pear Therapeutics (see DTx Case Study #5 for more information), have adopted a service provider business model in which the FDA-cleared DTx is bundled into a comprehensive service. With this related service, Pear Therapeutics offers a provider dashboard that displays aggregated insights and enables patients and clinicians to be in an informed, data-driven care partnership. This faster regulatory pathway may allow faster revenue generation by enabling a DTx to go to market with one level of effectiveness evidence. Subsequently, early usage data can then support the service and guide generate further enhancements, and also generate the additional evidence needed so that the DTx can later be approved as a stand-alone therapeutic product.

A combination therapy that uses DTx and traditional drugs can be very powerful

Although a DTx can compete directly with a traditional pharmaceutical in some disease areas, DTx is not a “pharma-killer.” Although DTx is accurately characterized as disruptive technology, its impact on the healthcare industry is similar to medical futurist Dr. Eric Topol’s take of the effect of artificial intelligence on medicine.

“It dawned on me that using technology to enhance humanity is the ultimate objective here…AI can restore the essential human element of medical practice by enabling machine support of tasks better suited for automation, thereby freeing doctors, nurses and other healthcare professionals to focus on providing real care for patients.”

— Dr. Eric Topol[6]

Using Topol’s approach, DTx can enhance current medical care by empowering clinicians with additional tools, and perhaps more importantly, robust data to better understand the individual behaviors and needs of each patient. Leveraging the power of technology can augment and enhance the human side of healthcare.

DTx can be prescribed along with traditional drugs and deliver powerful synergy that makes the combination of the two far greater in value than their individual parts. To borrow a military term, DTx can act as a force multiplier[7] for other treatments such as an individual drug by increasing patient understanding of medication adherence or assisting the patient to consistently adopt other behavioral or lifestyle changes that can further increase the effectiveness of the drug as part of an overall treatment. These hybrid, patient-centered care processes can improve health outcomes while avoiding more common and sometimes dangerous risks of unintended interactions that a combination of drugs can produce in the human body.

The following two case studies (Pear Therapeutics and Mahana Therapeutics) illustrate the potential synergies that could emerge from combining a DTx and an established, non-digital therapy.

DTx Case Study #5: reSET-O by Pear Therapeutics

reSET-O was the first prescription DTx to receive Breakthrough Designation and authorization by the FDA in December 2018.[8] reSET-O is a treatment for Opioid Use Disorder (OUD) that uses CBT alongside outpatient treatments, such as buprenorphine. reSET-O increases patient retention in OUD outpatient treatment programs. A comparative effectiveness study sponsored by Pear Therapeutics of patient retention rates showed that 82% of patients with OUD who received treatment with reSET-O stayed in treatment, versus 68% of those who did not have access to the DTx as part of their treatment[9] although another review of this research and other studies of DTx for OUD argued that the effectiveness data was not yet sufficient to endorse DTx for long-term obstinance and retention.[10] (This debate about studies of reSET-O is outside the scope of this eBook.)

reSET-O offers a provider dashboard that displays data on lessons completed by patients, patient-reported substance use, patient triggers, compliance awards, and clinic inputs, such as urine drug screen results. The amount of data available and the aggregated insights the clinicians can derive and share place patients and clinicians in a data-driven care partnership that could be more likely to achieve a positive outcome. Pear Therapeutics is a leader in prescription DTx and another example of leveraging one scalable digital platform for multiple therapies. Pear is continuing to enhance its platform, recently announcing collaborations to enable remote physiology monitoring[11] that can help it expand beyond the neurobehavioral market. Pear Therapeutics also has expertise in the regulatory process for digital technologies. One of nine companies selected as part of the FDA’s Digital Health Software Precertification (Pre-Cert) Pilot Program, Pear Therapeutics’ SomrystTM, an insomnia DTx, was recently approved via the Pre-Cert pathway.[12]

 

DTx Case Study #6: ParallelTM by Mahana Therapeutics

Mahana Therapeutics received de novo clearance from the FDA in November 2020 for Parallel, a CBT-based DTx focused on IBS.[13] As its name suggests, Parallel is not intended to be used as standalone therapy for IBS, but is instead used in conjunction with other treatments. Mahana recently announced a licensing agreement[14] with Kings College London for its 3-month prescription-only digital program that, in a randomized controlled trial showed, “substantial and durable IBS symptom severity improvements versus treatment as usual.”[15]

References for Chapter 4

1. Biopharmaceutical Research & Development: The Process Behind New Medicines. PhRMA. https://phrma-docs.phrma.org/sites/default/files/pdf/rd_brochure_022307.pdf. Published 2015. [Accessed September 29, 2021].

2. Akili Collaborates with Weill Cornell Medicine, New York-Presbyterian Hospital and Vanderbilt University Medical Center to Study Digital Therapeutic AKL-T01 as Treatment for COVID Brain Fog — Akili Interactive. Akili Interactive. https://www.akiliinteractive.com/news-collection/akili-collaborates-with-weill-cornell-medicine-newyork-presbyterian-hospital-and-vanderbilt-university-medical-center-to-study-digital-therapeutic-akl-t01-as-treatment-for-covid-brain-fog. Published 2021. Accessed August 20, 2021.

3. Akili Interactive. 2021. COVID Brain Fog — Akili Interactive. [online] Available at: <https://www.akiliinteractive.com/covid-brain-fog> Published 2021. [Accessed 19 August 2021].

4. Joyce M, Leclerc O, Westhues K, Xue H. https://www.mckinsey.com/industries/pharmaceuticals-and-medical-products/our-insights/digital-therapeutics-preparing-for-takeoff. Published 2018. [Accessed August 23, 2021].

5. Neeraj Sood P, Shih T, Karen Van Nuys P, Dana Goldman P. Flow of Money Through the Pharmaceutical Distribution System. USC Schaeffer. https://healthpolicy.usc.edu/research/flow-of-money-through-the-pharmaceutical-distribution-system/. Published 2017. [Accessed August 23, 2021].

6. Scripps.edu. 2021. Eric Topol pens book on artificial intelligence in medicine. [online] Available at:<https://www.scripps.edu/news-and-events/press-room/2019/20190312-topol-deep-medicine.html> [Accessed 19 August 2021].

7. “In military science, force multiplication or a force multiplier refers to a factor or a combination of factors that gives personnel or weapons (or other hardware) the ability to accomplish greater feats than without it. The expected size increase required to have the same effectiveness without that advantage is the multiplication factor. For example, if a certain technology like GPS enables a force to accomplish the same results of a force five times as large but without GPS.

8. Pear Therapeutics. 2021. reSET® & reSET-O® - Pear Therapeutics. [online] Available at: <https://peartherapeutics.com/products/reset-reset-o/> [Accessed 19 August 2021].

9. reSET-O & reSET |. 2021. reSET-O and reSET Clinical Evidence | reSET-O & reSET. [online] Available at: <https://www.resetforrecovery.com/outcomes/> [Accessed 19 August 2021].

10. ICER Publishes Final Evidence Report and Policy Recommendations for Digital Health Therapeutics for Opioid Use Disorder. ICER. https://icer.org/news-insights/press-releases/icer-publishes-final-evidence-report-and-policy-recommendations-for-digital-health-therapeutics-for-opioid-use-disorder/. Published July 13, 2021. [Accessed September 29, 2021].

11. Pear Therapeutics Expands Platform with Digital Biomarkers, Machine Learning Algorithms and Sensor-Based Technologies - Pear Therapeutics. Pear Therapeutics. https://peartherapeutics.com/pear-therapeutics-expands-platform-with-digital-biomarkers-machine-learning-algorithms-and-sensor-based-technologies/. Published 2021. [Accessed August 23, 2021].

12. MobiHealthNews. 2021. Q&A: A firsthand account of FDA's Pre-Cert Program. [online] Available at:<https://www.mobihealthnews.com/news/qa-firsthand-account-fdas-pre-cert-program> Published 2020. [Accessed 19 August 2021].

13. Accessdata.fda.gov. 2021. Device Classification Under Section 513(f)(2) (De Novo). [online] Available at:<https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/denovo.cfm?id=DEN200029> Published 2020. [Accessed 19 August 2021].

14. Mahana Therapeutics Enters Into Licensing Agreement With King's College London for Innovative Digital Therapeutic to Treat Gastrointestinal Condition. AP NEWS. https://apnews.com/press-release/pr-newswire/602a5329f3427608ddfc7f740ebb7f26. Published 2020. [Accessed August 23, 2021].

15. AP NEWS. 2021. Mahana Therapeutics Enters Into Licensing Agreement With King's College London for Innovative Digital Therapeutic to Treat Gastrointestinal Condition. [online] Available at: <https://apnews.com/press-release/pr-newswire/602a5329f3427608ddfc7f740ebb7f26> Published 2020. [Accessed 19 August 2021].

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