Welcome back to E&O Fridays, a paying subscribers-only weekly newsletter focused on the world of digital pharma products and FDA-regulated digital health.
E&O Fridays.
OK, here’s what’s happening this week in the world of pharma digital products and FDA-regulated digital health:
- Cognito Therapeutics shared results from its Phase II study and plans to move onto its pivotal study for its prescription digital therapeutic for Alzheimer’s. Here’s more about the PhII. (Remember: This one is a Breakthrough device and since it runs on its own hardware, it’s likely a lay-up for the new MCIT reimbursement pathway.)
- Mahana Therapeutics received a CE mark for its IBS-focused, prescription digital therapeutic, Parallel.
- Empatica also received a CE mark for its wearable device, Aura, which certifies that it can detect and alert wearers to respiratory infections (including COVID-19) “before visible symptoms appear.”
- Boehringer Ingelheim is kicking off a small, proof of concept study of a “digital behavior change intervention” for people with COPD. The intervention seems to be largely software-driven but the study will make use of Reemo Health’s software, which typically runs on Samsung smartwatches. BI used to have a high-profile partnership with Propeller Health, but there is no mention of Propeller in this study.
- The Celgene-Amalgam Rx study to evaluate the partners’ care platform for people with Multiple Myeloma is now recruiting patients. It also added trial sites in New York and Hawaii.
- Pear Therapeutics’ remote, nine-week insomnia treatment trial to collect RWD from Somryst users pushed back its likely completion date to 2025. Originally, it hoped to be completed by earlier this year. Pear is currently enrolling by invitation into this trial. It also loosened up its inclusion criteria to include people who get less than 6.5 hours of sleep each night. It also upped the anticipated enrollment number from 350 to 1,000 participants. The study’s researchers published its protocol in the medical literature this week too.
- Speaking of Pear: As I was digging into the Blues’ decision not to cover its PDTs for the story below, I did find a Medicaid plan in Pennsylvania that made the opposite decision. Gateway Health’s Medicaid members have coverage for Pear’s reSET-O and reSET as of August 2020. I’m not sure Pear announced this payer yet?
- One more thing… Huh. I had no idea there was an ISO standard in the works for health and wellness apps. (This is a rather serious attempt at that health app Holy Grail of a Good Housekeeping Seal of Approval that digital health keynoters talked up endlessly over the past decade.) Comments are open until mid-May so weigh-in now: “The new draft ISO standard (ISO TS 82304-2) proposes a set of 81 questions for app developers and manufacturers. Based on the answers and evidence provided the health app qualifies for a health app quality label with a score on four topics: Healthy and safe; Easy to use; Secure data; Robust build. The questions and the label with its color code support health professionals and users of apps to better select apps and app developers to better design apps.”
Editor: What’ll it be, stranger?
You (a non-paying-reader): Uh, I’ll have an… ice water.
[long-time E&O subscribers laugh]
Editor: Water? You want water, you better go dunk ya head in the horse trough out there.
[pulls out a shot glass and pours into it]
Editor: In here, we only serve paying subscribers.
Blues’ verdict on substance use disorder Rx digital therapeutics: Not enough evidence they work.
In last week’s Friday newsletter I was overly optimistic about a new, revised medical policy from Blue Cross Blue Shield of Massachusetts meant for “prescription digital therapeutics for substance abuse.” I wondered if it meant coverage was coming this June — quite the opposite.
As a few helpful readers wrote me following the newsletter’s publication (and as BCBSMA confirmed to me a few days after I asked about the document), the designation of “prescription digital therapeutics for substance abuse” as “investigational” meant the health plan would decidedly not be covering them based on the current evidence.
The email I received below from BCBSMA might read as unintentionally sweeping in its assessment of all prescription digital therapeutics on the market today, but it was in response to my query specifically about ones focused on substance use disorder (SUD):
“Blue Cross Blue Shield of Massachusetts is committed to ensuring the health and safety of our members by providing high-quality, affordable, evidence-based care. Our medical policy, based on accepted standards of care and evaluated regularly, currently classifies digital therapeutics as investigational. Our policy is consistent with that of the national Blue Cross Blue Shield Association.”
“At this time, there is not sufficient clinical evidence that the FDA-approved prescription digital therapeutics on the market meaningfully improve patients’ health in a lasting way.”
Still, the email noted that prescribers and patients have another route to push for coverage in individual cases:
“It’s important to note that our members and their physicians have the option of requesting a clinical exception to our medical policy. If that exception is denied, the member has the right to an appeal and an independent external review if an appeal is denied.”
The part about BCBSMA’s policy being in line with the national Blues association led me to seek out and find a number of similar policies from other Blues. Premera Blue Cross, for example, published its policy around prescription digital therapeutics in September 2020, around the same time ICER published its draft report. (Premera is the Blue plan for Washington state and Alaska.) Premera’s review of Pear’s evidence for reSET-O echoed a lot of what was in the ICER report. Premera wrote:
“…one of the trials assessed the combined intervention of computer-based learning and a reward for abstinence. Since reward for abstinence alone has been shown to increase both abstinence and retention, the contribution of the web-based program to the overall treatment effect cannot be determined. The treatment effect on abstinence was not observed at follow-up, raising further questions about the relative effects of the rewards and the web program.”
“The second trial, conducted in patients with primary opioid use disorder, did not meet a primary objective of longest days of abstinence. While both RCTs reported a positive effect on the intermediate outcome of retention, the relationship between retention and relevant health outcomes in these trials is uncertain.”
“In addition, both trials were conducted with an earlier technology (a desktop in a clinic) and were unblinded, so there are issues of possible performance bias and questions about generalizability of these results. Given all of these limitations, further study in well-designed trials is needed to determine the effects of prescription digital therapeutics on relevant outcomes in patients with substance use disorder and opioid use disorder. The evidence is insufficient to determine the effects of the technology on health outcomes.”
Blue Cross of Idaho had a similar assessment to Premera’s but it also dug into potential performance bias in the RCTs that Pear uses for reSET-O:
“An additional limitation is the potential for performance bias among the volunteers in these unblinded studies. Nearly half of patients who qualified for the Campbell et al (2014) study chose not to participate. There may have been greater motivation to use the new technology in patients who agreed to participate in the study.”
Blue Cross Blue Shield of Alabama issued a similar document that used the same analysis as the one BCI, above, used. So, as BCBSMA informed me — this seems to be a consensus position among the Blues.
Oshi-Takeda is one but which other digital health startups are pharma company spin-offs?
A lesser-known phenomenon in digital health is the pharmaceutical company digital health startup spin-off. My go-to example of this is Oshi Health, which is a virtual care clinic for people with gastrointestinal disorders. (It started out as more of a digital care program for GI disorders, but has since refocused to align with the growing virtual-first clinic trend.)
But even before Oshi was a digital care program, it was a concept incubated inside of a big pharmaceutical company: Takeda. Oshi doesn’t try to hide this fact, one of its co-founders Sona Chandra explains it on her personal site. From 2015 to 2018 Chandra was a Digital / Integrated Health Solution Engineer at Takeda Pharmaceuticals:
“What started as a role catalyzing the digital transformation across the company rapidly evolved into a digital health incubator. I was part of generating an idea through intensive healthcare stakeholder research and building an effective case around its product-market fit and business opportunity in order to win an investment from Takeda’s Executive Board to create and spin off the Oshi Health concept and product.”
I believe the Takeda-Oshi project was largely enabled by the team at BCG Digital Ventures. I’d like to start tracking these pharma spin-offs more closely, so hit reply and let me know if you are aware of others.
One final thought on these: I heard it said a few years ago that one additional reason pharma should consider these kinds of spin-offs is that the FDA treats startups differently from big pharma. The supposed benefits, according to this line of thinking, then, aren’t just about getting something built outside of the bureaucracy of a big pharma company, but perhaps a more forgiving and helpful FDA.
The second coming of ingestible event markers
So much of a startup’s success depends on timing and execution. There are a number of examples of high-profile startups that failed around the Dotcom crash, but had copycat companies that came along years later and built massive, billion-dollar companies with the same idea.
I always think about the failed Pets.com and its modern equivalent, Chewy, but the oft-cited example is probably Webvan and Instacart. There are countless of these in tech, but — so far — few (it any?) examples commonly cited for digital health.
All of that is to say: The high-profile failure of Proteus Digital Health has likely created a crater around the category of ingestible event markers, or sensor-equipped pills.
As I wrote in The Proteus Digital Health report last year, Proteus had a fast-follower in etectRx, which is now trying to navigate the world without its submarket’s one-time frontrunner. (Yes, yes — Proteus is now a part of Otsuka, but it’s been pretty quiet since joining up with its old partner.)
Did Proteus kill the category for the foreseeable future?
OK, yes, Instacart got its start fully 11 years after Webvan’s Chapter 11 bankruptcy filing, but tech takes much longer to find adoption in healthcare. So maybe the category winner is already operating today? Curious what you think.
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