Akili Interactive has created the medical equivalent of nutritious snack cakes. The company, based in Boston and San Francisco, develops video games that deliver sensory and motor stimuli engineered to treat conditions like ADHD, autism, depression, and MS. When Akili's first product comes to market following FDA approval, possibly by next year, doctors will prescribe it like medicine. But it is medicine that has no serious side effects, adapts to patients' functioning in real time, and is a pleasure to take. "That is not something that was in the world before," founder and CEO Eddie Martucci says.

Akili, which employs more than 80 people and has raised over $120 million since its founding in 2014, is part of the nascent field of digital therapeutics: technologies that produce real, measurable effects on medical disorders and disease. More than 100 companies in the United States and European Union, backed by around $2 billion in venture capital, have or are developing digital therapeutics, according to Marc Sluijs, founder of investment advisory group DigitalHealth.Network.

These are not your everyday diet and fitness apps. The companies comply with principles laid out by the Digital Therapeutics Alliance, an industry association. For example, they publish clinical outcomes in peer-reviewed journals, and undergo regulatory review of risk and efficacy claims.

"When we first approached the FDA, their response was, 'As long as you don't want to claim this as a treatment, you can sell something like it on the consumer market," Martucci says. "We said, 'You're not understanding our point. We want this to be a treatment. We want to hold ourselves to a very high bar to make sure we can claim that.'"

A game-changing game

Akili's first product treats children with ADHD. The pediatric market is appealing because of its size--ADHD has been diagnosed in 6.4 million children in the U.S.--and because of parents' concerns about children taking drugs. Other digital therapeutics companies target everything from diabetes and Alzheimer's to chronic back pain and sleep disorders. 

Akili has run several clinical trials on its software, a racing game called Project Evo that plays on smartphones and tablets. Patients maneuver their avatars down a fast-moving river. As obstacles pop up, they must quickly choose whether to tap, catch, or avoid them. "It is tailored in a personalized fashion to push the bounds of the frontal processing system of the brain dealing with complex information," Martucci explains.

The trials showed improvements in cognition, symptoms, and daily functioning. In some domains, Akili's digital approach was in the range of what drugs can achieve. In others, the product was somewhat less effective. But it remains far safer than pharmaceuticals. "We don't think about this as, it is better or worse," Martucci says. "For some patients, your standard care, Ritalin, will continue to be the most important option. For a lot of other patients, we believe that what we have provides the best treatment." In some cases, he expects, digital therapeutics and drugs will be prescribed together.

Scott Kollins, director of the ADHD program at Duke University and a paid consultant for Akili, ran a proof-of-concept study on the company's product four years ago, and more recently oversaw a larger trial. He points out that digital therapeutics offer an advantage for patients who live far from doctors skilled in behavior therapy. They also have the potential to provide results not possible with ADHD medication, which he likens to glasses that help you see better but don't affect the underlying condition. "One thing that is intriguing, though we don't know this yet, is whether something like Akili's product can be disease-modifying, where you are engaging circuits in the brain in a manner that changes their function over time," Kollins says.

When drugs aren't the answer

As a doctoral student at Yale, Martucci researched ways to find drugs by looking at physiological targets in the body. The lure of entrepreneurship drew him to PureTech Health, where he became a principal, forming companies around health care innovations.

Martucci 's team was looking at the needs of patients with conditions related to the brain. Drug development in areas like pediatric behavior disorders and depression was expensive, with high failure rates. And drugs weren't necessarily the best answer. "Some chunk of any population can't take pharmacology," Martucci says. "Another chunk of patients just refused. They don't want to go on traditional medication with these conditions."

It was 2010, and two things were happening. Neuroscientists were learning to produce changes in the brain by activating targeted sections. And smartphones and tablets were becoming ubiquitous. Those developments helped shaped Akili. The company's first four products employ an algorithm created by co-founder Adam Gazzaley, a neuroscientist at the University of California, San Francisco. Meanwhile another co-founder, Matt Omernick, spent more than eight years as art director at LucasArts, working on Star Wars games and other projects. "In the early days we had investors ask, 'What are you really investing in, science or clinical trails or entertainment?'" Martucci says. "I said, to maximize the impact this can have on the brain, [and to get] people excited by our type of medicine, you need to invest in everything."

A business model in progress

Experts predict that in five years, digital therapeutics will be accepted as a normal weapon in doctors' arsenals. But there remains a steep learning curve for physicians and insurers. Key to the industry's success will be pricing. The inclination may be to treat software as a cheaper option than physical medicines. But "as digital therapies generate clinical outcomes that are comparable with drugs, you could argue that it should be priced higher than a drug," says Sluijs of DigitalHealth.Network. "Not only are there no side effects, but there is a huge benefit to collecting a lot of data about behavior and outcomes."

Another question mark is the role of large drug companies, which, through acquisitions, licensing arrangements, and internal development, could simply add digital therapies to their portfolios. "The pharma industry is starting to become very active in this sector, both as an investor and a partner," Sluijs says.

Akili has no immediate plans to seek pharmaceutical companies' help marketing its products to doctors. The company is building out its own prescription and reimbursement system and wants to own its relationships with providers and, especially, with patients.

"We know that most people don't know or care who makes their medicine," Martucci says. "By providing a product that is safe and fun and wonderful to use, we are creating a connection with the patient."

Published on: Dec 4, 2018