Medtronic announces CE-Marking for Guardian 4 sensor CGM and connected insulin pen InPen – May 26, 2021

Guardian 4 Sensor

Guardian 4 offers users fingerstick free CGM with “self-calibration” and non-adjunctive labeling; integrations with MiniMed 780G and InPen; maintains form factor and 7-day wear of Guardian Sensor 3

Medtronic’s Guardian 4 (f.k.a. Zeus) is the company’s first consumer CGM approved for fingerstick- and calibration-free use. The device is indicated for patients ages 7+ years old. Guardian 4 builds on Medtronic’s existing Guardian Sensor 3 CGM system: it keeps the same form-factor and seven-day wear, but removes fingerstick calibrations via a novel “self-calibrating” mechanism. Additionally, Guardian 4 comes with non-adjunctive labeling, meaning patients can dose insulin directly off of CGM values without performing a confirmatory fingerstick. This marks a significant improvement over Guardian Sensor 3 which required two calibrations per day, as well as confirmatory fingersticks. Guardian 4 has a two-hour warm-up time, same as Guardian Sensor 3. Guardian 4 will also offer patients predictive low and high glucose alerts similarly to Guardian Sensor 3 and will be integrated with Medtronic’s MiniMed 780G Advanced Hybrid Closed Loop system, which received CE-marking in June 2020 and was launched in October 2020. Guardian Sensor 4 users will also be able to integrate their CGM with InPen to create a closed data loop for patients on MDI. A similar data integration was announced for US InPen and Guardian Sensor 3 users in November, giving patients access to their Guardian Connect data directly in the InPen app in real-time. According to comments from Medtronic, Guardian Sensor 4 will begin to roll-out in Europe “this fall,” which is also when patients will gain access to these updated integrated systems.

• This fall, the European CGM market will likely see increased competition with Abbott’s continued roll-out of FreeStyle Libre 3 and Dexcom’s plans to submit G7 for CE-mark in the near future. That said, Medtronic certainly has a strong user base in Europe and the ability to offer users a fingerstick free non-adjunctive experience may help attract new users, especially for patients interested in the MiniMed 780G Hybrid Closed Loop System. Additionally, for current MDI users, the option to integrate CGM and insulin dosing data from InPen may also prove to be an attractive option.

• On the US front, Guardian 4 was submitted to the FDA both as a stand-alone CGM in October and as part of the MiniMed 780G system as of Medtronic’s 4Q20 update. At this point we have not received any approval timelines from Medtronic, and it is unclear if the FDA will prioritize the stand-alone submission or the MiniMed 780G submission which could impact approval timing. However, comments from Medtronic suggest that Guardian 4 may meet the accuracy requirements for an iCGM approval which would make it the first of Medtronic’s sensors to have that labeling. That said, Medtronic has previously stated that interoperability is not a priority in its diabetes business, not too surprising, as Medtronic is currently the only company able to offer users a fully in-house AID system. We imagine it may also be that iCGM designation does appear to some to be not completely clear – that is our opinion only at this moment and certainly does not take away from enormous work and achievements that have gone into related achievements on this important, growing, and dynamic front. Medtronic has plans to share Guardian 4 data at ATTD 2021 which may help address questions around iCGM accuracy standards and US approval/launch timing.

Feature Comparisons between FreeStyle Libre 3, FreeStyle Libre 2, Dexcom G6, G7, Medtronic Guardian Sensor 3, and Guardian 4 Sensor

In this first table, we’ve summarized the key features of Abbott’s FreeStyle Libre 2, Dexcom’s G6, Medtronic’s Guardian Sensor 3, and the new Guardian 4 sensor. The specific features and indications represent general European availability. The yellow highlight denotes which system(s) has the advantage on a particular category; of course, this is our opinion, and some is subjective!

In this second table, we’ve compared the key features of the newest standalone CGMs approved in Europe from Abbott, Medtronic, and Senseonics, as well as Dexcom’s G7 (CE submission expected soon). For Dexcom G7, we’ve made certain assumptions about the product features based on publicly available data and statements as the device is not on the market. The yellow highlight denotes which system(s) has the advantage on a particular category; of course, this is our opinion, and some is subjective!

InPen

European launch of InPen expected “this fall”; approved for use in all ages and in patients over seven when paired with Guardian 4

With today’s CE-Marking for InPen, Medtronic plans to bring InPen to Europe “this fall.” A previous version of InPen was actually CE-Marked in 2018, but Companion Medical never launched the device in Europe. As a reminder, InPen (available in the US since 2017) offers users a connected smart pen experience with a reusable pen lasting for 1 year that tracks insulin dose and timing and monitors insulin temperature. InPen also offers users a bolus calculator via its connected InPen App (Android, iOS) based on insulin on board, carb ratios, meal estimations, and fixed dosing regimens. Per our conversations with Medtronic, InPen’s most recent CE-Mark takes into account updates made to the system since 2018, including data integration with Guardian CGMs that will now also be available with the Guardian 4 CGM when it rolls-out in Europe this fall. This CGM and insulin dosing data integration allows patients to see “real-time glucose readings and alerts alongside insulin dose information” all from within the InPen app in combined glucose and dosing reports that can also be shared with health care providers. InPen’s CE-Mark does not have a specific age indication, but stipulates that users under seven require supervision. Medtronic has moved quickly to expand access to InPen since acquiring Companion Medical in August 2020, and from our view, is certainly taking advantage of the opportunity to expand its user base into patients on MDI.

• Smart pens continue to be the talk of 2021 especially in Europe where Novo Nordisk has recently launched its NovoPen 6 and NovoPen Echo Plus smart pens in Sweden and Denmark. At this point Novo Nordisk has CGM data integration agreements with Abbott, Dexcom, and Medtronic, but these integrations are not yet launched and likely won’t be real-time even after launch. Looking ahead, we’re also curious to gauge Medtronic’s interest in supporting data integration with a direct competitor. (Medtronic and Novo Nordisk signed their data integration agreement preior to Medtronic’s Companion Medical acquisition.) That said, InPen relies on compatibility with NovoLog cartridges (in addition to Fiasp), so there are certainly incentives for Medtronic to continue working closely with Novo Nordisk. While Lilly and others are currently working to bring their own smart pen technology to market, other smart pens available in Europe include Biocorp’s Mallya, Pendiq’s reusable pen, Emperra’s ESYSTA smart pen, Insulclock’s smart cap – to our knowledge, none of these devices have gained significant market traction.

What’s Next for Medtronic?

MiniMed 780G & Guardian Sensor 4 in the US

As a reminder, MiniMed 780G has been submitted to the FDA as of February, but the approval timeline has not been disclosed. The submission combined adult and pediatric data, as well as Medtronic’s previously submitted Guardian 4 (f.k.a. “Zeus”) CGM to provide the FDA “with an efficient means to simultaneously review [Medtronic’s] multiple submissions.” That’s an incredible advantage for Medtronic in our view. Presumably, this is a strategy suggested in the company’s conversations with the FDA to reduce the number of submissions the FDA must review and minimize any delays due to COVID-19 related back-log. Given the delays around the FDA, Medtronic is not providing any timelines for approval or launch of MiniMed 780G in the US. However, we look forward to (hopefully) hearing updates on the timeline during tomorrow’s 1Q21 (F4Q21) earnings call.

Closing the loop for patients on MDI: Integrating InPen with AI-powered meal detection technologies, Nutrino and Klue, and next-gen Synergy CGM

Medtronic plans to use its various technologies across AI, CGM, and insulin delivery to “close the loop” for patients with MDI. Specifically, based on commentary at Medtronic’s Analyst Day in October, the company is working to combine InPen with its AI-powered meal detection acquisitions, Nutrino and Klue, to make it easier for patients to determine their optimal meal dose without carb counting. At its Analyst Day, Medtronic also shared plans to integrate InPen with Guardian 4 (check! √) and with its next-gen Synergy CGM, which may be submitted to the FDA in the near future (more on this below). Together, these integrations would simply the diabetes self-management experience for patients on MDI, providing some of the benefits of AID systems to those not using insulin pumps.

Slide taken from Medtronic’s Analyst Day

Next-gen, fully disposable Synergy CGM in the US (and OUS?)

Based on the timeline shared in February, Medtronic will submit its next-gen, fully disposable CGM, “Synergy,” to the FDA following the completion of its “manufacturing module this summer.” As a reminder, Synergy is Medtronic’s first fully disposable sensor and has a form factor about 50% smaller than Medtronic’s current Guardian Sensor 3. Medtronic is targeting seven-day wear for Synergy, as well as “self-calibration” (like Guardian 4) based on commentary from October. The timeline for an OUS regulatory process for Synergy has yet to be disclosed, but now that Guardian 4 has made it through the process, it seems likely that Medtronic will move ahead with efforts to get Synergy approval in OUS markets.

Slide taken from Medtronic’s Analyst Day

--by Hanna Gutow, Katie Mahoney, Albert Cai, and Kelly Close