After years of waiting, Akili Interactive has finally received FDA De Novo marketing authorization for EndeavorRx, its video-game digital therapeutic for children aged 8 to 12 years with ADHD.

This is the first game-based therapeutic that the FDA has greenlit for any condition, the regulatory agency noted in its announcement. It is also the first authorization for Akili, which has a handful of similar software therapeutic products in its development pipeline.

Previously known as Project: Evo and AKL-T01, the EndeavorRx software treatment is indicated by the agency to improve children's symptoms associated with ADHD, and is intended for use as one component of a broader therapeutic program addressing these symptoms.

The therapeutic takes the form of a game in which users navigate an alien avatar through a course while they respond to on-screen prompts. The app keeps track of movements and so can monitor the user’s behavior and quickly adapt to the player.

“We’re proud to make history today with FDA’s decision," Eddie Martucci, ECO of Akili, said in a statement. “With EndeavorRx, we’re using technology to help treat a condition in an entirely new way as we directly target neurological function through medicine that feels like entertainment. Families are looking for new ways to help their children with ADHD. With today’s decision by FDA, we’re excited to offer families a first-of-its-kind non-drug treatment option and take an important first step toward our goal to help all people living with cognitive issues.”

Akili said in the statement that EndeavorRx "will be available with a prescription to families soon" as part of the company's Endeavor Care Program, which includes, alongside the therapeutic app, a behavior-tracking app for parents called ADHD Insight and a direct line to caregiver support services called Akili Assist.

However, a nonprescription form of the digital therapeutic is already being distributed by the company thanks to an emergency policy from the FDA allowing digital products for to be temporarily released before a more formal approval. That rollout provided the first look at the Akili Assist offerings and a general idea of the company's long-touted, pharma-free distribution and commercialization strategy.

WHAT'S THE IMPACT?

To make its decision, the FDA said that it reviewed trial data from multiple studies and more than 600 patients – chief among which was the STARS-ADHD pivotal trial that was concluded in late 2017 and published in full just a few months ago.

Across this and other studies, the agency said that it looked for clear improvements in attention function. No serious adverse events were reported among any of the studies, according to the FDA. However, frustration, headache, dizziness, emotional reaction and aggression were all reported in the studies as common adverse events.

The data and the De Novo clearance pave the way for a new modality of ADHD treatment that clinicians can consider as an alternative, or addition to, drug-based treatments and other efforts.

“The EndeavorRx device offers a non-drug option for improving symptoms associated with ADHD in children and is an important example of the growing field of digital therapy and digital therapeutics,” Dr. Jeffrey Shuren, director of the FDA’s Center for Devices and Radiological Health, said in a statement. “The FDA is committed to providing regulatory pathways that enable patients' timely access to safe and effective innovative digital therapeutics.”

Beyond the benefits of EndeavorRx itself, the De Novo clearance opens up a regulatory pathway for upcoming software therapies for ADHD, and more broadly sets a precedent for game-based products as vetted, evidence-based treatments.

THE LARGER TREND

The regulatory victory has been a long time coming for Akili, which first confirmed that it was moving forward with an FDA submission for what was then known as Project: Evo back in 2017. The two-and-a-half years since came with relatively few updates from the company, with a couple of notable exceptions.

In January of 2019, Martucci drew a line in the sand separating Akili from the broader trend of digital therapeutics companies partnering with established pharmas to distribute their products. At the time, a representative confirmed that the company was working on "a very different type of commercial model than traditional pharma" for its ADHD therapeutic and following products. That work largely appears to have taken the form of the distribution and support resources available as part of the Endeavor Care Program.

When the company published its pivotal trial in The Lancet Digital Health journal earlier this year, Dr. Anil Jina, chief medical officer at Akili, noted that the company faced some difficulty building an appropriate control for its video-game-based treatment, which could have complicated EndeavorRx's case for efficacy. He also acknowledged some "timeline frustration" within the company as it awaited a final decision from the FDA, but still was sympathetic to the regulatory challenges of approving such a product.

The De Novo clearance is a feather in the cap for Akili, which was already recognized within the digital therapeutics space as a frontrunner in video game medical treatments, but it's not the only company combining biofeedback and games to drive behavioral health treatments.

Barcelona-based Braingaze announced plans to launch its ADHD therapy app in the Chinese market, while another company called ATENTIV has worked to test its ADHD intervention in Singapore and the U.S. Mightier, a Boston Children's Hospital spinout, has also pulled in money from investors for its biofeedback video games designed to help children with emotional regulation.