Editor's note: This story has been updated with quotes and additional information from Mahana's CEO and cofounder.

The FDA has granted a De Novo clearance to San Francisco-based Mahana Therapeutics' Parallel, a prescription digital therapeutic for patients with irritable bowel syndrome (IBS) that delivers cognitive behavioral therapy (CBT).

The agency made its decision on November 25, according to an FDA listing updated on Monday. Mahana submitted the application back in April.

Parallel was first developed by researchers from King's College London under the name Regul8 over the course of about 15 years, Mahana CEO and cofounder Rob Paull told MobiHealthNews. The startup struck a worldwide exclusive licensing agreement with the institution last year, he said, although word of the deal wasn't announced until January 2020.

The three-month digital treatment logs a patient's symptoms and uses them to deliver relevant guidance. In addition, the digital CBT teaches patients skills and habits to help them manage their condition.

Parallel is intended to reduce the severity of IBS symptoms among adults aged 22 years or older who have received a diabnosis. It is a combination treatment alongside other IBS medications.

Paull also said that he will be stepping aside as the company's CEO to make room for Steven Basta. The new executive comes with 20 years of commercial medical technology background, having most recently served as CEO, president and director of Menlo Therapeutics (now VYNE Therapeutics). Paull will stay on as a member of Mahana's board.

WHAT'S THE IMPACT?

Per the International Foundation for Gastrointestinal Disorders, IBS affects somewhere between 25 million and 45 million people in the U.S. Their symptoms can range in severity from inconvenience to debilitation, and roughly 20% to 40% of gastroenterologist visits are due to IBS symptoms.

To seek its clearance, Paull said the company leaned on a 558-person randomized, controlled trial published last year in the BMJ's Gut. Here, researchers compared symptom and social-function capabilities among IBS patients given CBT over the phone from a therapist, CBT through the digital therapeutic with minimal therapist support, or treatment as usual.

While outcomes were strongest among patients receiving support from a live therapist, those who received the digital treatment with minimal human support also demonstrated significant improvements in both study measures after 12 months. Adverse events were few across all groups, and none were related to the intervention itself.

Mahana's website also highlights a study of the treatment published in The Lancet Gastroenterology & Hepatology in September 2019. A longitudinal analysis of participants from the prior study, it saw sustained improvements among participants through the 24-month follow-up period.

Paull noted that although human-delivered CBT had a greater impact in both versions of the study, the company's goal is "absolutely not" to position its treatment as a replacement for live therapy.

"Part of the opportunity or unmet need that Mahana is trying to address is that for the 35 to 40 million people who are suffering IBS just here in the U.S. alone, ... there's only about 260 therapists or psycologists who are trained in gastrointestinal disorders," he said. "What Mahana is trying to do is fill an important void that is complementary to face-to-face psychotherapy, complementary to medication, to provide a clinically validated – now FDA-cleared – treatment that could be scalable. Because it's software based, it could be therefore accessible to millions of patients."

While Mahana took the licensing route for its first product, Paull said the company's primary primary focus going forward will be building up a pipeline of gastrointestinal therapeutics internally, starting with a program focused on inflammatory bowel disease.

For these conditions, the CDC's most recent incidence data suggests about 3 million adults reported an IBD diagnosis in 2015. According to a 2019 study, mean hospitalization costs for Crohn's disease and ulcerative colitis were $11,345 and $13,412, respectively. Many patients also report a reduced quality of life and negative psychological impact or negative attitudes due to these conditions.

With that being said, he didn't rule out another licensing agreement if the right candidate came to light. 

"I would say we have a hybrid approach," he said. "If we find a clinically validated digital therapeutic out there, we may be interested in licensing it. But right now Mahana is interested in building a pipeline of its own products."

THE LARGER TREND

It's been a big year for digital therapeutics, both in terms of regulation and market opportunity.

Parallel marks the third such product to receive the FDA's De Novo clearance, following Akili's video game-like ADHD symptom treatment EndeavorRx in June and NightWare's smartwatch and phone app for improving sleep quality among those with nightmare disorder or related PTSD.

Beyond these, Pear Therapeutics' Somryst for insomnia picked up a 510(k) in March and temporarily rolled out its experimental digital therapeutic for schizophrenia in light of the ongoing COVID-19 crisis. Swedish pharma company Orexo took a similar approach as well, deploying its digital treatments for depression symptoms and problematic alcohol use on a limited basis.

Leaders from several of these companies and other stakeholders have said that COVID-19 has created a uniquely opportune landscape for digital therapeutics to thrive. Specifically, they cited the shift away from in-person services, the high demand for behavioral health therapies, broader digital health exposure and the increased employment of decentralized digital trials as major contributors to the niche industry's progress.

"There's this open moment because of COVID where everyone is aligned. Patients are desperate and want solutions. Providers see that these walls are broken down, and they want to respond," Eddie Martucci, CEO of Akili Interactive, said during a digital therapeutics panel discussion in September. "Everyone understands that we have this taste of efficiency and rapid ability to serve the patient, and we're seeing it happen in real time. I certainly hope that pace cements itself and doesn't recede."