January 11, 2023 | Digital therapeutics (DTx) are a natural fit with the decentralized clinical trial (DCT) model and the COVID-19 pandemic has been a major driver of demand for both. The hybrid-designed PROSPER-FM trial is a good case in point. The devices being studied are a digital Acceptance and Commitment Therapy (ACT) program and digital symptom tracker for adults with fibromyalgia, a surprisingly common and chronic affliction, and the single virtual site, run by Curavit, has been enrolling 10 times more patients than all other bricks-and-mortar sites starting at the same time.

That’s what’s being reported in a status update on the trial by Mike Rosenbluth, Ph.D., CEO of sponsor Swing Therapeutics and Joel Morse, cofounder CEO of Curavit, the world’s first all-virtual contract research organization (CRO). They agree that inclusion of the virtual site is proving to be a great way to broaden access to the study and enhance diversity while improving participant engagement overall.

The hybrid approach was a “smart strategy” by Swing, allowing the startup to balance the risk of betting on the wrong distribution channel before the evidence was in, says Morse. The virtual approach is still new and, understandably, the industry wants to see the data demonstrating its efficacy.

It’s looking good so far, says Rosenbluth, and not just in terms of enrollment. Participants are also staying in the trial and adhering to the protocol. The risk going in was that patients enrolled remotely could be less engaged and thus less likely to know, and do, what they’re supposed to. That the opposite has happened has been “really interesting.”

The enrollees recruited remotely include notoriously hard-to-reach populations, notably Native Americans located nowhere near a physical site, Morse says. Part of the trick is doing the upfront work of making the entire process virtual so individuals can truly participate in the trial from the comfort of their home.

Curavit, like Swing Therapeutics, is a young company. It was founded in early 2020—right before COVID-19 was declared a pandemic—to focus on DCTs, says Morse. Previously, he founded a company called C3i (sold to Merck in 2014 and subsequently purchased by HCL Technologies Limited) that grew into a $100 million global firm that split its time on global clinical trial execution and pharmaceutical commercial services.

That gave Morse 15 years of experience building out the service offering of Quintiles (now IQVIA), then C3i’s biggest client, as well as all of Medidata’s tier 1 and some of their tier 2 global core services. During this period, he also had plenty of practice running global clinical trials for sponsor companies big and small.

After getting his Ph.D. in biomedical engineering, Rosenbluth blazed his career path in early-stage venture investing with a focus on startup medical device and biopharma companies. Swing’s acting chief medical officer was also responsible for the last drug (milnacipran) approved for fibromyalgia in 2009, he notes.

Stanza, the prescription digital therapy app designed to deliver behavioral therapy to people with fibromyalgia, is the lead product of Swing Therapeutics, founded in 2019. But the company is also exploring other therapeutic areas, including several autoimmune diseases, where digital therapeutics can make a difference.

Scaling Treatment 

The prescription DTx under investigation in the PROSPER-FM trial provides an innovative form of behavioral and cognitive therapy that is a first-line treatment for fibromyalgia, a widespread pain condition affecting 10 million people in the U.S. In addition to chronic pain, afflicted individuals can suffer from a host of comorbidities such as disturbed sleep, difficulty concentrating, and mental health impacts that include depression and anxiety, explains Rosenbluth.

Three drugs for treating fibromyalgia have been approved by the U.S. Food and Drug Administration (FDA): pregabalin (Lyrica, Pfizer), duloxetine HCL (Cymbalta, Eli Lilly), and milnacipran (Savella, Forest Labs/Cypress Bioscience). Prescription drug therapies have widely varying degrees of effectiveness but, even if they work, many patients opt to stop taking these drugs within a year because of intolerable side effects, Rosenbluth says.

In  a public meeting with the FDA, patients reported that non-pharmacological approaches proved more reliably effective. Cognitive behavioral therapy with ACT—the aim of which is to help people accept their feelings as they are and commit to taking useful action in line with their personal values—has also been scientifically demonstrated to have positive effects on pain-related functioning, mental health-related quality of life, self-efficacy, depression, and anxiety (European Journal of PainDOI: 10.1002/j.1532-2149.2012.00224.x)

Scaling this “very specialized treatment” to accommodate the large population of patients with the disease has been the main challenge, says Rosenbluth. Swing’s answer was to develop a smartphone-based application to deliver the treatment digitally. And it received a Breakthrough Device designation from the FDA in hopes of more quickly bringing the product to market by creating an open, ongoing dialogue with the agency to ensure the evidence being built with the PROSPER-FM trial aligns with regulatory expectations of a submission package.

Prescription DTx are regulated as medical devices under the FDA’s Software as a Medical Device program, Rosenbluth says. Nine such devices have been approved to date.

Protocol Reengineering 

The 12-week PROSPER-FM study started in February 2022 with 25 physical sites and a goal of enrolling up to 300 participants, says Rosenbluth. Participation requires six patient visits, and the primary endpoint is patient global impression of change per electronic patient-reported outcomes.

The study is expected to finish enrollment in the first quarter of 2023, Rosenbluth continues. Curavit was added to the mix in August with the expectation that its digital outreach approach would expand access to a broader patient population than would typically participate in clinical research by virtue of geography.

Adding a virtual site required making a few adjustments to the study workflow, says Morse. This most notably included reengineering of the one-step screening process requiring a urine drug screen and confirmation by the principal investigator (rheumatologist) that a would-be participant has fibromyalgia. For remote participants, the three-step procedure is for clinical research coordinators to conduct a 90-minute telehealth visit to screen individuals (eliminating half of the pool of prospects), who then go to a nearby drug center with a QR code to get a urine drug screen and subsequently have a televisit with the rheumatologist (again cutting the patient pool by 50%).

The changes were necessary for the virtual part of the trial to work to ensure appropriate individuals were enrolled as well as remove unnecessary burdens on patients, Morse says. Other than better reaching several underserved populations, he adds, people enrolled remotely looked very similar to those enrolled by the bricks-and-mortar sites. But, overall, they interacted more with the virtual site than their counterparts enrolled at a traditional research site.

While the virtual site has certainly augmented enrollment, the bricks-and-mortar locations are likewise indispensable when it comes to ensuring diversity, Rosenbluth says. “We are also relying on sites that are very experienced in conducting fibromyalgia studies and can help all the sites as they learn from each other, and Curavit has been able to take advantage of some of those learnings, too.”

From the FDA’s standpoint, a chief concern with remotely enrolling participants is identify verification, which represented a protocol amendment, says Rosenbluth. But, broadly speaking, the agency views DCTs favorably due to its interest in equitably expanding trial access.

The DTx industry, through regulatory guidelines and with the support of the Digital Therapeutics Alliance, is “working hard” to ensure its collective voice is heard with the FDA, Morse adds. “Frankly, regulators have been very open to hearing that voice and partnering… for the good of everyone.”

It’s a group that would be difficult to ignore. The global DTx market, valued at $42 billion in 2021, is projected to reach $56 billion over the next five years with an estimated compound annual growth rate of 26.1%.

In the U.S., the DTx market is expected to hit $11.2 billion by 2030. One of the drivers has been the FDA’s pandemic-related fast-tracking of commercial availability for prescription DTx products for treating patients with psychiatric conditions under the agency’s Enforcement Policy for Digital Health Devices during the COVID-19 Public Health Emergency, says Rosenbluth.

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