PLUS: A Wittgenstein’s Ladder reference

Issue 080

 E&O Fridays.

Welcome back. Two weeks ago in E&O Fridays, I speculated about the Amwell-Omada price tag (I think we’ll hear about this deal around JPM), dug into kickbacks and digital health, and recapped a busy week for Pear Therapeutics.

And if you missed Monday’s newsletter — it was sort of a slow week because of the Thanksgiving holiday here in the US — just $99 million in funding (announced and unannounced). I also revealed the answer to the latest Health Tech Trivia question along with an impressive group of contestants who answered correctly.

Finally, last Wednesday, for E&O’s enrollment-focused digital health newsletter, I dug into a new Fortune 500 Digital Health Stack: Activision Blizzard‘s. I also wrote about the slow-motion unraveling of Livongo‘s CVS partnership and a few big customers that Hinge Health is enrolling right now.

OK, here’s what’s happening this week in the world of digital pharma products and FDA-regulated digital health:

• I published a new searchable, sortable database of the six (and counting) digital health products that have secured reimbursement via the German government’s DiGA program this year. As the list grows and some of them get removed, I figured it would be handy to have this on the site.
• On that note: Yesterday, Germany added Invirto, a VR-based prescription digital therapeutic for various panic disorders, to DiGA. It runs about $520 all-in (app, headphones, VR headset).
• Dthera 2.0? A new prescription digital therapeutics startup, Neuroglee, emerged (https://techcrunch.com/2020/12/02/neuroglee-gets-2-3-million-to-develop-digital-therapeutics-for-neurodegenerative-diseases/) this week with a $2.3 million pre-seed round. Japan pharmaco Eisai led the round and Biofourmis CEO and Founder Kuldeep Singh Rajput contributed too (Neuroglee is his brother’s company). Singapore-based Neuroglee, which has an initial focus on Alzheimer’s, intends “to treat patients in the early stages of the disease.”
• Meanwhile, Click Therapeutics raised (https://news.yahoo.com/click-therapeutics-secures-30m-growth-140000336.html) $30 million in debt financing from K2 HealthVentures. Click’s last equity raise was back in mid-July when it raised $17 million led by Sanofi.
• Kaia Health, perhaps best known for its work in digital MSK, inked (https://www.chiesi.com/en/kaia-health-and-chiesi-group-announce-strategic-partnership-to-commercialise-kaia-copd-pulmonary-rehabilitation-app-in-european-markets/) an exclusive commercialization deal with Italian pharmaco Chiesi Group, to commercialize Kaia’s COPD pulmonary rehab app in Europe: “The agreement marks one of the first times in respiratory care that a digital therapeutics company and pharmaceutical company are partnering to bring patients a digital therapeutic that supports COPD treatment outcomes through behaviour change, rather than relying on pharmacology.”
• FDA cleared Braid Health’s “AI-powered diagnostic collaboration software.” It’s a mobile app that: “lets providers and radiologists access, review, and annotate images and share results with patients in realtime — from any mobile device. With integrated AI for quality assurance, the software also helps providers avoid errors and ensure interpretations are highly accurate.”
• Signant Health acquired (https://www.prnewswire.com/news-releases/signant-health-acquires-virtrial-to-enhance-its-digital-enablement-of-clinical-research-sites-and-evidence-generation-capabilities-301181547.html) VirTrial, which offers software for remote sites and decentralized clinical trials.
• This 23-page report (https://www.pwc.com.au/health/National-Digital-Mental-Health-Framework_Consultation-Paper.pdf) from PwC scopes out what a National Digital Mental Health Network might look like for the Australian government.
• The UK’s NICE just published (https://www.businesswire.com/news/home/20201201005522/en/iRhythm-Technologies-Receives-Positive-National-Guidance-in-First-of-its-Kind-Digital-Health-Pilot-with-National-Institute-for-Health-and-Care-Excellence) a positive review of cardiac monitoring company iRhythm’s wearable-powered service. It was the first to go through a new digital health pilot NICE has set up.
• One more thing… In Europe, Novo Nordisk is now allowing (https://developer.novonordisk.com/) digital health developers to pull in data from its newest smart insulin pens: “Once you register and have signed the agreement for use of the pen specifications and potentially a data-sharing agreement, you will receive documentation to guide you in establishing a connection between your app, device or system and NovoPen 6 and/or NovoPen Echo Plus.”

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FDA grants De Novo clearance to Mahana Therapeutics for IBS-focused Rx digital therapeutic

Mahana Therapeutics, which was founded just three years ago, has secured a De Novo clearance from the FDA for Parallel, a prescription digital therapeutic (PDT) for irritable bowel syndrome. Mahana submitted to the FDA in late April, which means its De Novo time-to-clearance was about seven months.

(That’s only 7 times slower than Apple’s!)

While that’s not Apple-fast, it is unusual for a three-year-old startup to secure a De Novo clearance so soon after its founding. How has it moved so quickly? Well, Mahana seems to be hewing closely to Pear Therapeutics’ playbook.

(Jeremy Gilbert, formerly of Pear, is Mahana’s acting Chief Strategy Officer.)

Mahana’s PDT, Parallel, is an 8-week program. It was formerly known as Regul8, a web-based CBT program developed by Rona Moss-Morris PhD, Head of Psychology Department, King’s College London. While Mahana is early-stage, Regul8 is no spring chicken.

If you recall way back in Issue 035, when the licensing deal became public, I included this quote from Regul8’s British inventors: “We spent over 18 years developing and clinically testing a personalized digital CBT program for adult IBS patients.”

While Parallel has never been studied, its predecessor Regul8 has been over the years. Here’s how Mahana touts Parallel’s outcomes on its site right under the heading “Parallel Clinical Trial”:

The ACTIB trial was actually a three-arm one that included CBT via telephone calls, CBT via web (that’s the Regul8 arm), and treatment as usual. The telephone arm showed better results than the other two, but the web-based version was significantly more cost-effective.

At 12 months, the IBS Symptom Severity Score was 61.6 points lower in the telephone CBT arm and 35.2 points lower in the web CBT arm than in the treatment as usual arm. For the other primary outcome measure, it was closer. The mean Work and Social Adjustment Scale score at 12 months was 10.8 in the treatment as usual arm, 3.5 points lower in the telephone CBT arm and 3.0 points lower in the web CBT arm.

Finally, the web-version was significantly more cost-effective than the telephone CBT: “The incremental cost-effectiveness ratio (ICER) (QALY) for TCBT versus TAU was £22,284 and for WCBT versus TAU was £7724.”

The ACTIB trial took place between May 2014 and March 2016. So, it ended almost two years before Mahana Therapeutics started up.

Anyway, that’s a long-winded way of pointing out that Mahana is likely to face some of the same problems that Pear did if ICER decides to dig into digital CBT treatments for IBS. ICER didn’t take Pear’s evidence base seriously. The organization argued that the predecessor web-version of the reSET-O therapeutic, TES, which was administered at an on-site clinic, was not the same therapeutic as Pear’s mobile version of the program even though the content was nearly identical. UPDATE: Mahana’s Parallel is actually a web-based program just like its predecessor. I was assuming it was a mobile version of its web-based predecessor (like Pear’s set-up) when I wrote this.

Navel-gazers, unite: Digital vaccines (oh boy), Rx digital therapeutics, and middle management

OK, bear with me. I’m generally reluctant to wade into these terminology debates, but it’s getting close to the end of the year, and it may be helpful to sharpen this a little bit more. A recent article in MobiHealthNews referenced and linked to E&O’s Prescription Digital Therapeutics Database, and a few different companies wrote to me to ask why they weren’t in there.

In most discussions, it seems like the controversial piece of the PDT puzzle now is whether or not a product needs to include a “treatment” claim in its label to qualify. If that’s confusing, let’s start here: This definition that I found in a recent Blue Note Therapeutics job listing is pretty close to how I think of PDTs (minus an adverb or two)…

The Digital Therapeutics Alliance also makes a distinction between companies that make a “treat” claim and those that make a “manage” claim or a “prevent” claim in their marketing. Here’s a chart from a recent letter the DTA sent to CMS:

As is often the case, the letter starts out by making clear that digital therapeutics “are distinct from the over 350,000 digital health apps available online.” This is a years-old rallying cry now that is probably only helpful to laggards (not to say there aren’t many of those in healthcare, CMS included).

Digital therapeutics, as a carved-out, however, still ends up being an incredibly diverse mix of businesses. The term is increasingly too imprecise to be helpful as a category.

Prescription Digital Therapeutics (PDTs)

The E&O PDT Pipeline of Pipelines Database is an attempt to track this slice of the category. It will increasingly adhere to the Blue Note definition listed above. As some of the products in the pipeline reveal more of their go-to-market plans, I might have to remove them from the database. In most cases, these therapeutics are trying to go to market as a pharmaceutical therapeutic would. This is the “Everything But the Drug” go-to-market strategy for DTx. Pear, Akili, Cognoa, Mahana, Blue Note, and many others are in this category.

Prevention and “digital vaccines” (groan)

At the other end of the digital therapeutics spectrum, we find claims that use the term “prevent” in a sometimes successful attempt to distinguish programs from simple wellness or fitness programs that look similar but maybe don’t have the same clinical evidence backing them up.

At least one digital health company, FriendsLearn, is working to get the term “digital vaccine” into circulation alongside digital therapeutic. FriendsLearn developed a video game, called fooya!, that it describes as “a pediatric dietary mobile game” today. It hopes to be able to call it a “digital vaccine” for obesity someday.

Here’s FriendsLearn’s Founder and CEO Bhargav Sri Prakash:

A few weeks ago, JMIR publication of a small RCT (104 kids) on the effects of fooya.

Whatever it ends up being called, this “prevent” category is clearly distinct from the “treat” category.

In the middle: Disease management

This is where it gets blurry. Digital health companies with FDA-clearances that include a “manage a disease” claim, generally, do not want to be seen as different from those that “treat” a disease. Typically, however, these clearances show the product is intended for remote monitoring or clinical decision support (the patient’s decisions and/or the provider’s).

As the DTA chart above makes clear, the products in this category only sometimes require an Rx. That typically is the case when the risk is higher. Clinical decision support tools like insulin titration algorithms will trigger the Rx requirement, for example, in a diabetes management program.

Many of the big players in chronic disease management (Livongo, Omada, Vida, Lark, One Drop, etc.) have largely eschewed the digital therapeutics label in recent years. Some of them are, instead, opting to embrace virtual care and while evolving into full-stack virtual clinics.

Thought experiment: If a company like Virta Health ever went to the agency (why would they though?) and sought an FDA clearance for some of the claims it makes around “reversing” diabetes via a keto diet, I think that would end up being a “treatment” claim, if they ever got it through.

Where it goes next: Kick the ladder

These three digital therapeutics subcategories will continue to grow apart. It won’t be useful to refer to this evidence-backed carve-out of the world of 350,000 health apps (a number that hasn’t changed in three years somehow?) for much longer.

Like Wittgenstein’s ladder, this was a helpful construction in 2019 and 2020, but it’s time to shelve the unmodified, catch-all term “digital therapeutic” in the new year.

That’s a wrap on Issue 080 of E&O Fridays.