After nearly a decade of work, Akili Interactive received the green light from the FDA to market its video game as a treatment for ADHD. It wasn’t an easy feat, and the company still has a long road ahead to get physicians and insurers to adopt its product.
“There are not a lot of words to describe it,” Akili CEO and Co-Founder Eddie Martucci said in a phone interview the day after the FDA cleared its product. “We’ve been in a mode of just proving out everything we have.”
Martucci, a principal at PureTech Ventures with a background in pharmacology, teamed up with former LucasArts Executive Art Director Matthew Omernick and UC San Francisco neuroscientist Dr. Adam Gazzaley to start the company in 2011. At the time, most of the big pharmaceutical companies were backing away from neuroscience.
It was also when people began carrying around smartphones.
“From day one, we were really taken with the concept that technology could deliver medicine directly. Games became a natural vehicle for us as we looked at best ways to deploy sensory and motor stimulus,” Martucci said. “We saw that need. We saw that there was nothing new. We said, if we’re going to bring something new, let’s go really dramatic.”
A big Endeavor
Akili first submitted clinical data from a pivotal trial of its video game treatment two years ago. The company sought clearance through the FDA’s de novo pathway, a regulatory process for new medical devices that are deemed low- to moderate-risk.
The company’s first product, EndeavorRx, was cleared on Monday to improve attention in children ages 8 to 12 with ADHD. The game challenges users to collect specific targets while navigating frozen rivers and lava lakes.
“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 news release.
Akili licensed the core technology behind the game out of Dr. Gazzaley’s lab. The game constantly adjusts as the user’s skill improves and is designed to provide challenges that activate the neural systems that play a key role in attention.
After building the initial set of algorithms, the company spent the last seven years running more than 30 clinical trials of the technology. The biggest of them was a double-blind, randomized controlled trial of 348 patients.
How do you design a clinical trial for a video game?
“There were so many complexities. It was the first time we were trying to study an interactive treatment,” Martucci said. “People would say you can’t study interactive digital treatments like medicine and you can’t get FDA approval for something like this. We disagreed with both.”
One of the challenges is designing a control. If the device is intended to be used with another treatment, such as medication, the control group could receive their regular medication while the investigational group could receive both the medication and the device.
Or, a “placebo” game could be used.
“Some people do better because someone is checking in with them. You try to control for those effects,” Manatt Health Partner Yarmela Pavlovic said in a phone interview. “You create a game or an app that isn’t expected to have a therapeutic effect but would replicate people spending time on a given activity.”
This is the approach that Akili took. The company partnered with Duke University to create a randomization scheme. Patients received a tablet with either Akili’s game or the control — a digital word game.
Results of the trial showed patients that played Akili’s game showed a statistically significant improvement in attention compared to the control, measured using the Test of Variables of Attention (TOVA).
“We basically had to invent some of the blinding protocols. People would not know which treatment they were on,” Martucci said. “It’s one of the things we’re really proud of.”
The regulatory milestone also created a new category of digital health devices, which the FDA refers to a “digital therapy device for ADHD.” In the future, other companies with similar games will be able to file with the FDA for 510(k) clearance.
The next level
Our course, Akili’s journey is far from over. The next level will be to capture the interest of physicians and insurance companies.
As hard as it is to get FDA clearance, “In the end, I think the hardest part is getting reimbursement and distribution,” said Lisa Suennen, leader of Manatt’s digital and technology group, and its venture capital fund.
Akili plans to have its game prescribed like a medicine. A physician would write a prescription and the patient would receive an access code. They would then download EndeavorRx and use that code to activate the game.
One of the challenges is that there isn’t much of a system in place for this yet. Doctors can’t prescribe digital therapeutics on a pad.
More work will be needed to get insurers on board. Although they’re becoming more familiar with digital health products, as evidenced by Express Scripts’ first digital health formulary, it’s still not an easy sell.
“They’re perfectly happy to look. You have to do your work to figure out how to prove it to them within their own context,” Suennen said. “They usually want you to do a study with them. They want evidence that’s more directly relevant before they go far with it.”
Martucci had no illusions about this.
“The insurance community is always a battle for new products. We don’t anticipate it will be covered on day one,” he said. “Our goal has always been that this is a prescribed medicine, and it should be covered for patients. I don’t think it’s far off and we’re certainly committed.”
Akili may have gotten a small head start after the FDA temporarily loosened some regulations around digital health products in April due to the Covid-19 pandemic. Martucci said Akili did a limited release of EndeavorRx under this guidance.
“During that process, an early limited launch phase, we’ve been able to engage with the prescriber community,” he said. “Doctors care deeply about the data and about their patients. If they can look at the data, they support it.”