Understanding Innovations and Challenges in Prescription Digital Therapeutics: An Insider's Perspective

In an interview with First Report Managed Care, Eddie Martucci, PhD, cofounder and CEO of Akili Interactive offers insight into the evolving prescription digital therapeutics (PDTs) landscape. 

Please share some background information about the development of your company’s prescription digital therapeutics. 

Akili set out more than a decade ago to develop digital treatments that were different than what you see in the market today. A vast majority of digital therapeutics are human practices, like behavioral therapies that are put into an app. We wanted to do something dramatically different. 

We wanted to make treatments that were a little more “medicine” in nature, meaning they activated pathways in the body that were dysfunctional or needed direct treatment. We wanted to make treatments that were engaging and leveraged everything it means to have a consumer digital product in front of you. We took both of those elements—the concepts of deep physiological stimulation and entertainment-style experiences—and melded them together. 
Our digital therapeutics are clinically validated medical treatments that are delivered as video games. These products do not teach you strategies to deal with your life. Instead, they directly activate the parts of the brain that control cognitive functioning. 

Our first product, EndeavorRX, is a prescription digital therapeutic for children with attention deficit/hyperactivity disorder (ADHD). When children use the video game, it stimulates the part of their brain that controls attention. We also just recently released a product called EndeavorOTC, which is an over-the-counter version of that product meant for adults with ADHD, so it can be purchased directly. This is the angle we want: something that feels like entertainment but stimulates your brain in such a way that it has a big therapeutic effect.

How are PDTs being used to improve cognitive impairments and neurodevelopmental disorders?

What is interesting to think about when it comes to neurodevelopmental or psychiatric disorders is that, for a long time, we have treated some of the more overt symptomologies of the conditions with medication. For instance, in depression, the medications target sadness and mood. In ADHD, people often turn to medication for behavioral problems and hyperactivity.

The “silent issues” of these behavioral health conditions often have been left behind in many patient populations, including children all the way up through adults. These are the cognitive issues that are not necessarily manifesting in an obvious way, but the patient is really struggling with. You cannot necessarily notice attention, memory, or speed of processing just by interacting with someone for a few minutes. But these things are massive quality-of-life impediments and a major limiting factor in successful treatment in tens of millions of people with different conditions.

Digital therapeutics and PDTs, like EndeavorRX and EndeavorOTC, are designed to target directly and precisely at those cognitive functions instead of flooding the brain for a range of issues and hoping to achieve cognitive improvements. The beauty of digital therapeutics is they can be tailored and targeted in such a way that you do not necessarily touch a patient’s personality. While you do not necessarily touch mood and other behaviors, you can home in on the cognitive issues that people are dealing with and magnify the improvements. That type of personalized, targeted, specific treatment is what PDTs are capable of, for improving cognition and more.

For forever, people with ADHD have said, "I'm not really getting the full treatment I need." One of the biggest things we heard early on was, "I don't want to have to sacrifice my personality or my creativity by taking medication." Often, people will feel empowered by using PDTs, saying, "I can improve my attention, but it's now on demand. I'm not on drugs or off drugs, I just improve my attention by using this product. And now I can use that attention how I please without sacrificing other parts of me." 

In your opinion, what areas of PDT development have been most successful?

I think the areas that have been the most successful in PDT development have been clinical and regulatory validation. When I started Akili, when this field was being born about a decade ago, people had legitimate questions: Can these products work? And even if they work, can they be validated like other medical products? That was a real question in people's minds because running clinical trial programs with something that feels like a video game is not trivial. We had to invent how to do that.

But now we have seen about a dozen PDTs that are very different. Some, like ours, are video games; some are behavioral therapies; and some are other formats that have been through clinical trials, demonstrated clinical outcomes, published in medical journals, and approved by the US Food and Drug Administration (FDA). In one decade, it is huge to go from "We don't even know if this is possible," to, "Of course, it's possible. And there are now multiple products, in multiple populations and multiple indications, that are on the market and being prescribed by doctors because we can validate that the products work." That is massive progress. I think what has happened in this field has laid the groundwork to have dozens to hundreds of products over the next decade.

What are the greatest challenges of PDT development in the industry today? 

Unquestionably, the biggest challenge to PDT development and growth is insurance coverage. There is no doubt about it. Patients often fear that the insurance industry is not willing to be innovative and cover products that are safe for them. In the case of PDTs, that is true. The insurance industry has been very slow to adopt PDTs.

Drugs are covered almost ubiquitously, but for these safe digital treatments, it is still taking a very long time for insurers to create a coverage framework so these products can be offered to millions of Americans at scale. Until that happens, there will be a whole lot of patients that are without these safe digital treatments. But I do see it moving. It is just not moving at the pace that I, as an entrepreneur, want, or that most patients want.

How have the development, testing, and deployment processes of PDTs changed since you initially started working with PDTs? 

When we started in the industry, people took a very linear, even sequential drug-like approach to validation. We certainly did. You would run a small-scale study and then a slightly larger-scale study, and then a large, pivotal, randomized, controlled study, maybe a few of them. And then you would go to the FDA, make it a prescription-only product, and scale it. That is how the first handful of products, including EndeavorRX, came to be. 

I think what has changed is that people have realized that is a really long process for a digital product. Digital is always changing. Every 6 months, the newest digital technologies have evolved dramatically. Because these products are safe, we can do better, frankly, in this industry. 

What has evolved the most is people becoming flexible with how they think about study design and data collection, like running parallel studies or putting a product out to collect real-world evidence to use as validation and bring that product to market. 

Also, the business model experimentation has really expanded. For instance, we could have gone the same pathway for our adult product as we did with our pediatric product, but we decided the need was so great and we knew how these products worked in the market, so we put out an over-the-counter product without the need for a prescription for adults. So we are seeing experimentation on the clinical side and on the business model side, and that is really good for patients.