From Close Concerns Diabetes Technology Meeting Highlights
Revealed: Dexcom G6 Accuracy vs. iCGM Special Controls (high bar indeed); G6 Enhancements for 14-Day Wear, 1-hr Warmup, New Adhesive, Less Lag; Vagueness on Verily; TypeZero Next-Gen Algorithm Work
Dexcom VP Mr. Peter Simpson shared a number of never-before-seen slides, including G6’s accuracy stacked up against the iCGM special controls and data on next-gen enhancements to G6: 14-day wear and 1-hour warmup (still sub-10% MARD, >90% of points within 20/20), a new adhesive that propels ~90% of sensors lasting 14 days (up from ~75% now), and reduced time lag down to 2.5 minutes vs. YSI (currently ~4 minutes). Vagueness on the fully disposable Verily sensor continues, with just a side profile picture shown this time around without any scale comparator – less detail than we got two years ago at DTM, and it remains unclear if two Verily generations will launch. We also heard about new TypeZero/Dexcom work on a next-gen closed-loop algorithm, which will enable simplified/no meal announcement, a more aggressive and personalized algorithm to optimize time-in-range, and a simplified system startup. Dexcom and TypeZero are also joining forces on MDI decision support, including a trend-based bolus calculator and more dosing guidance. Many slides and details are enclosed below!
- For the first time since G6 launched, we got to see the sensor’s accuracy stacked up against the iCGM special controls – 95% lower confidence bound finally included for all glucose bins. The G6 label does not actually share the confidence intervals around the point estimates, so this was a long-needed slide. The takeaway remains the same, as Mr. Simpson noted: “FDA has set a very high bar for accuracy.” However, it’s now even clearer just how high that bar is, since G6 barely crosses the thresholds in some areas. (One could more easily argue now that these controls were designed around G6, and like any line drawn in the sand, there is some arbitrariness here – e.g., why “87%” and not “86%” for within 20%?) This slide also reminds us that using the lower bound of the 95% confidence interval raises the bar even higher, since it requires: (i) a point estimate that exceeds the threshold by a meaningful margin; or (ii) a study large enough that the confidence interval is closely aligned to the point accuracy. All in all, it’s clear that Abbott and Medtronic are not likely to obtain iCGM accuracy standards unless they can make leaps forward in sensor accuracy. Senseonics may meet the bar with Eversense, though it is prioritizing 180-day wear first.
- Mr. Simpson also shared brand-new G6 platform enhancement data, starting with an n=78 trial of 1-hour startup and 14-day wear. The data look quite good, with MARD still under 10% – including between hour 1-2 – and 91.9%-93.7% of points within 20% of 20 mg/dl. Only data from hours 1-2, day 10, and day 14 were presented, so we’re not sure what the aggregate performance looks like. Adam asked in Q&A about whether this data meets the iCGM standard, and Mr. Simpson clarified that the study was not powered to adequately answer that question; indeed, far more patients/paired points would be needed to get tight enough confidence intervals, especially with the above in mind. Dexcom’s 3Q18 call had not confirmed this trial’s completion, which clearly occurred well within the original plans for “2H18.” CEO Kevin Sayer said Dexcom will first get its new adhesive (see below) ready before moving to 14-day wear, so this enhancement sounds like a mid/late-2019 launch at the earliest – assuming a larger trial confirms 14-day/1-hour G6 still meets the iCGM accuracy benchmarks. For context, G6 currently has an overall MARD of 9.0% and overall 94% of points within 20/20, with a day 1 MARD of 9.3% and 91.1% within 20/20; the below looks right on par.
In our view, this is among the most important enhancements to G6, since it would match FreeStyle Libre’s updated wear/warmup time. (Libre 14-day launched in late October in the US following FDA approval in July.) Plus, a 14-day wear G6 would give Dexcom more pricing cushion and better margins, reducing sensors from three down to two per month.
Mr. Simpson also showed new data (n=24) from a “high reliability patch” for G6, which prompts an ~20% relative increase in 14-day sensor survival vs. the current adhesive – per the graph below, ~75% of current G6 patches survive to 14 days, which increases to ~90% with the next-gen adhesive. No further details or timing were shared, though this seems like an excellent and necessary upgrade. On the 3Q18 call, CEO Kevin Sayer shared that this new G6 adhesive is coming out in the “not-too-distant future.” We’d guess sometime in 2019 at this stage, though it was not specified. The size of the patch skirt looks unchanged, so presumably this changes the stickiness or materials. We’re not sure if this patch will reduce skin reactions, which can prevent some from using CGM. On Thursday at DTM, 3M noted the hard tradeoffs that come with adhesive, since improving on one dimension (stickiness) often comes at the expense of others (irritation).
- Dexcom is also working on further reducing G6’s sensor time lag vs. YSI, which is ~4 minutes now and ~2.5 minutes with the next-gen version. The data was marked as unpublished and For context, the G4 platinum had a 6.5 minute lag, G4 with software 505 brought it down to 5.7 minutes, and G5 brought it down to 5 minutes. In Q&A, a comment noted that even if the current G6 lag was zero, it could still be up to five minutes (maximum) since readings only display in five-minute intervals; reducing updates to every minute would help the user experience on the lag front. Of course, that would also demand more battery life to relay Bluetooth reading, so the tradeoff is not quite that simple!
- Regarding the next-gen disposable CGM with Verily, Dexcom is “not quite ready to show the final design,” but Mr. Simpson did show a profile of the very thin wearable. It looks quite slim, as expected, but there was no size comparator, making it hard to know just how thin it is (e.g., is it the originally planned penny-sized thickness?). This was the only Verily device shown, and it was unclear if this was the first- or second-gen version; we assume the latter, which has the low-cost advantage, the next-gen sensor, and is still under development. As of Dexcom’s 3Q18 call, the company was “considering options” for the gen one Verily device (using current G6), and the smaller, low-cost, second-gen device was slated for “late 2020/early 2021.” Dexcom’s upcoming investor day on December 4 should hopefully give more specifics on the Verily plans.
- Citing the acquisition of TypeZero, Mr. Simpson noted the team is already working on a next-gen closed loop algorithm with “full automation” (no meal announcement!), simplified startup and meal announcements, optimization to increase time-in-range, and personalized delivery based on a patient’s data signature. Seeing both “meal announcement” and “no meal announcement” implied to us that the system will integrate manual meal announcement when a user does so, though it will be able to cope without it – perhaps via more aggressive automated correction boluses. The first-gen version of this algorithm is in its pivotal trial within Tandem’s Control-IQ system, slated for a summer 2019 launch.
- TypeZero/Dexcom continue to work on better tools for MDI users, including a trend-adjusted bolus calculator, actionable insights, smart pen integration, and both real-time and retrospective therapy guidance. No timing was shared in this talk. The 3Q18 call said pilots of this technology are ongoing, with a broader commercial rollout “certainly by 2020.” Dr. Marc Breton’s talk on Day #2 gave a great overview of the technology, which is leaps better than the guidance MDI users have now.