Memorandum

Medtronic Sentrino critical care CGM receives CE Mark; controlled European rollout to begin immediately with UK and Germany – December 3, 2012

Executive Highlights

  • Medtronic’s Sentrino critical care CGM system has received CE Mark approval. The device incorporates redundant sensing (two subcutaneous sensors), a cable, and a bedside monitor.
  • A controlled rollout of Sentrino will occur in Europe starting immediately in the UK and Germany. Medtronic is working with FDA to support US commercialization, though there is no timeline yet.

This morning, Medtronic announced that its critical care CGM system, Sentrino, received CE Mark approval. A controlled rollout will occur in hospitals across Europe, beginning immediately with the UK and Germany. The Sentrino CGM system includes redundant sensing technology (two novel subcutaneous sensors; neither Sof-Sensor nor Enlite), a processor cable (to connect the sensor with the monitor and temporarily store data during disconnection), and a bedside monitor that provides glucose values, trends, and predictive alarms and alerts. Patients can wear the Sentrino for up to 72 hours before the sensors need to be replaced. The Sentrino is accurate within 10-15% of reference glucose and is approved for adjunctive use. The device is calibrated using the hospital’s standard of care blood glucose measurement. Warm-up time is 30 minutes (pretty fast!) and a blood glucose calibration is required upon insertion, at one hour, two hours, eight hours, and then every eight hours thereafter. One hundred patients were studied prior to CE Mark submission, and 50 of them were critically ill patients.

The press release announcing the CE Mark specifically notes that Sentrino is an “investigational device only in the US and not approved for sale in the US.” Medtronic is working closely with the FDA on plans to support US approval, though there is no current timeline. If Dexcom management’s comments during the recent 3Q12 earnings are a guide, we suspect Medtronic is still waiting on FDA to weigh in on the acceptable approval criteria for an in-hospital CGM. As a reminder, there is also no current US timeline for Dexcom/Edwards’ second-generation GlucoClear critical care intravenous CGM – while CE mark for that device is still expected before year-end, discussions with FDA are not expected until 2013. Given that Medicare has declared “Manifestations of poor control of blood sugar levels” a “never event” (no reimbursement), we believe there will be lots of enthusiasm for in-hospital CGM in the US.

We hope today’s European approval marks an increasing trend of more CGM devices in the hospital. Notably, Medtronic believes the critical care CGM market will exceed $1 billion globally. Given the challenges of managing glucose in the inpatient setting (especially in critically ill patients), we believe CGM will dramatically help providers keep patients in target more often, especially for reducing the risk of hypoglycemia. Certainly, the additional real time data, trending information, and predictive alarms will represent a major improvement over periodic glucose checks every two to four hours. We’re not sure how much the Sentrino costs, though that will be key to watch as hospitals weigh the huge added value of more glucose information against tightening budgets. Another key factor is how in-hospital CGM will affect nursing time – we are not sure ultimately how much more or less nursing time will be required vs. current standard-of-care (e.g., another device; more initial blood glucose checks, but ultimately), but feel patients should unquestionably benefit. What’s more, we suspect clinical outcomes and recovery time will improve as patients spend more time in euglycemia, meaning hospitals could increase turnover and reduce lengths of stay – the magic words that are loved by every administrator.

  • While few details about Medtronic’s Sentrino critical care CGM have been shared, we look forward to learning more as the device launches. The minor details we know are noted below.
    • Redundant sensing technology: Sentrino relies on two subcutaneous sensors for more accurate visibility of glycemic variability. These are new sensors, meaning neither the Sof-Sensor nor Enlite. The design uses multiple channels and the system evaluates the best signals, combining them to create a more accurate glucose value and minimize errant values.
    • Subcutaneous: The sensor has been “customized for the critical care patient and inserts quickly and easily with low complication rates.” Assuming the accuracy is good, this represents an important advantage over intravenous CGMs in development.
    • Drug interference rejection technology: This feature ensures minimal interference with the wide array of pharmaceuticals used in the critical care unit.
    • Integration with clinical workflow: The press release notes that the Sentrino “integrates simply into clinical workflow” – we suspect this means integration with hospital electronic medical records through wireless connection or some other standardized protocols.
  • Based on the pictures of the device (enclosed below), the monitor does an impressive job of using colors to quickly indicate glycemic status. It looks as though the monitor and sensor are connected via a wire, though since these are critical care patients that are not likely ambulating, we don’t see this as a big limitation. However, we expect if future generations target general hospital floors, wireless transmission would need to be incorporated.
  • At this stage, there are a number of companies working on development of in- hospital CGM products. The list below is certainly not exhaustive – it is informed by our coverage of the field and companies present at the FDA in-hospital CGM meeting in June 2012.

Company

Product

Level of Invasiveness (Sensor)

Target Market

Recently Reported MARD**

Recently Reported Timeline

 

Medtronic

 

Sentrino

 

Redundant Subcutaneous (Glucose Oxidase)

 

Critical Care

 

10-15%

 

CE Marked; controlled EU launch to start immediately in Germany and the UK

 

Echo Therapeutics

 

Symphony

 

Transdermal (Glucose Oxidase)

 

Critical Care

 

9% - 12.3%

 

EU launch in 2H13; US trial to commence in 2013.

Dexcom/Edwards

GlucoClear 2

Intravenous (Glucose Oxidase)

Critical Care

5.2%

CE Mark by end of 2012; FDA discussions in 2013

Dexcom Gen 6 Subcutaneous (Glucose Oxidase) Hospital "very highly single-digit"  ?
GluMetrics GluCath Intravascular (Optical) Critical Care 7.5% ?
Maquet Eirus Intravascular (Dialysis) Critical Care 5.9% CE Marked in April 2011
OptiScan OptiScanner Intravenous (Optical) Critical Care  <4% CE Marked in September 2011

** MARDs are very difficult to compare due to vast differences in study design, calibration techniques, population, etc. However, we find it broadly useful to include them to get a better sense of where companies stand. The reported MARDs are from the recent FDA in-hospital CGM meeting (see below), recent company earnings calls, posters on company websites, or recent conferences.

  • As we noted in our recent report from the FDA’s in-hospital CGM meeting, the Agency made it clear they would not be issuing formal guidelines for hospital CGMs. Instead, the FDA plans to evaluate submissions based on risk-benefit profiles. FDA’s tone was generally positive throughout the day despite clear uncertainty in certain areas. Panelists could not agree on the performance metrics FDA should use to evaluate in-hospital CGMs, although there was general consensus that the accuracy bar is lower for a tracking/trending device (adjunctive) vs. a device use to dose insulin (replacement). Yet, panelists did not uniformly agree on the minimum acceptable accuracy requirements for each. A positive for all the companies in the arena was the view that there is room for a range of different CGM devices approved for different indications and even different patient populations. For our full commentary on the FDA Public Meeting, please see https://closeconcerns.box.com/s/a5ifxblh2vvxqzdhxsxt.

Close Concerns Questions

Q: How will clinicians and hospitals make the accuracy/invasiveness tradeoff? What will be the deciding factor – rate of infections, overall accuracy, something else?

Q: What level of CGM accuracy would be required for a blood glucose meter replacement claim?

Q: How much does Sentrino cost?

Q: How challenging will it be to secure reimbursement for in-hospital CGM?

Q: How long was the review process from submission to CE Mark approval? How much did the trials cost? How long and real world were the trials supporting approval?

Q: When will we see broad use of in-hospital CGM in the US and Europe? What will be the biggest barrier – reimbursement, device design/quality, provider perceptions of hassle, lack of positive outcomes data?

Q: Is critical care CGM truly a $1 billion global market (as Medtronic says)?

-- by Adam Brown and Kelly Close