Abbott receives CE Mark for FreeStyle Libre Flash Glucose Monitoring System – September 3, 2014

This morning, Abbott announced that it received CE Mark for its 14-day wear, factory calibrated FreeStyle Libre Flash Glucose Monitoring system. The timing is right on par with the company’s 2Q14 call and marks less than one year since the novel glucose monitoring product concept was unveiled at EASD 2013. FreeStyle Libre will be available in France, Germany, Italy, the Netherlands, Spain, Sweden and the UK in the coming weeks. It will also be available for purchase online through a website in each market (Abbott already has the website www.freestylelibre.co.uk running, though US users cannot access it).

We assume the product will not launch with significant reimbursement, and that once more real-world clinical studies are completed, Abbott would work to secure reimbursement from European payers. We believe the value of the product will be significant as strong adherence should help outcomes, perhaps dramatically (early users in the EU with whom we have spoken love it and say their patients look at it frequently, which prompts greater success in numbers).  FreeStyle Libre is approved in Europe for anyone with diabetes; however, we expect the initial focus to be on insulin users, especially on MDIs whether they are type 1 or type 2. That said, we believe patients anywhere on the diabetes continuum (and, in fact, pre-diabetes continuum) will be able to show significant benefit. As noted in the company’s 2Q14 call, follow-on Flash Glucose Monitoring products will target other segments of the market.

Through conference updates over the past year (EASD 2013, DTM 2013, IDF 2013, and ATTD 2014), Abbott has given us an excellent feel for the system, and there are few additional details in the press release beyond what we’ve already reported (see first bullet below). The announcement emphasized the product’s factory calibration (and by association, insulin dosing claim), a significant advance that eliminates the need to calibrate the sensor with fingerstick readings in most cases – this is a particularly impressive engineering and manufacturing feat given the 14-day wear. Similar to the FreeStyle Navigator’s label, however, FreeStyle Libre readings will need to be confirmed with a fingerstick in a few specific cases: during times of rapidly changing glucose levels; if hypoglycemia/impending hypoglycemia is reported by the system; or when symptoms do not match the product’s readings. Details from Abbott’s CE Mark study, including accuracy data, will be shared in its upcoming EASD symposium on September 15 (available via webcast). In prior studies we’ve seen, the 14-day, factory calibrated sensor has demonstrated an MARD of ~9%-11% (see below).

Given the low current rates of CGM penetration worldwide, we are optimistic that this new glucose monitoring category can help patients monitor more frequently; help make clinicians’ lives easier; and help save the healthcare system money in the long-run. There is no current timeline on a US submission, though Abbott management has said that FreeStyle Libre will be a global product, and it will come to the US. The major question in the US concerns obtaining an insulin dosing claim, something Dexcom is also discussing with the FDA.

• Today’s announcement shared a few new details about FreeStyle Libre that we had not previously known: (i) FreeStyle Libre is approved for wear on the upper arm; (ii) for the reader to scan the sensor and download the glucose data, it must be within 1-4 cm; (iii) the subcutaneous sensor is 5 mm long and 0.4 mm wide.
• As a reminder, Abbott’s FreeStyle Libre Flash Glucose Monitoring concept was first introduced at EASD 2013. The idea is to overcome some of the limitations of both BGM (pain, inconsistent and hard to interpret data) and CGM (fingerstick calibration, cost, alarm fatigue). The approved system consists of a touchscreen reader (similar in look to the FreeStyle InsuLinx meter) and a small, round sensor patch the size of a two Euro coin worn on the back of the upper arm – see the picture below. The patch measures glucose every minute in interstitial fluid through a factory calibrated 14-day, subcutaneous sensor (5 mm long, 0.4 mm wide) held in place with a small adhesive pad. A reader is scanned over the sensor (within 1-4 cm; works through clothing) to obtain a real-time glucose reading, eight-hour trend graph, and glucose rate of change arrow in less than one second. The reader holds up to 90 days of data and downloads to the Ambulatory Glucose Profile, a single-page download intended to make glucose data analysis easier for both healthcare professionals and patients. The system software is both Mac and PC compatible.
• While FreeStyle Libre could give “CGM-like” data if someone “scanned” the reader over the sensor every five minutes, we believe it is more likely to be used to get intermittent data quite easily (i.e., no fingerstick, no blood, and what sounds like little hassle). We don’t expect to see many traditional CGM users switching to this new system (FreeStyle Libre does not have alarms), though we do think it will help expand the continuous glucose sensing market, particularly in type 2 diabetes. In addition, we wonder if follow-on Flash Glucose Monitoring products could be targeted at current CGM users.
• Abbott will host a symposium “Ambulatory Glucose Profile (AGP) and New Sensor Technology” at EASD 2014, featuring the new FreeStyle Libre – notably, it will be webcast for those not attending. Indeed, you can sign up to watch here – the webcasting is unprecedented, we believe, and we like the idea of many people being able to access early information, even if they can’t afford to be there live. Dr. Irl Hirsch (University of Washington, Seattle, WA) will present on the clinical value of sensor-based glucose monitoring, Dr. Ramzi Ajjan (University of Leeds, Leeds, UK) will present on clinical case studies of type 1 and type 2 diabetes from the SIGN study (we assume these were the studies of FreeStyle Libre that were mentioned at ATTD), Dr. Stefano Genovese (IRCCS MultiMedica, Sesto San Giovanni, Italy) on the clinical use of Flash Glucose Monitoring, and Mr. Jared Watkin (Divisional Vice President, R&D, Abbott Diabetes Care, San Francisco, CA) with a Flash Glucose Monitoring update. The latter has provided the biggest news at Abbott’s most recent symposiums (ATTD 2014, IDF 2013, EASD 2013), and we expect this iteration will be no exception. 
• Said Abbott Diabetes Care esteemed SVP Robert Ford in today’s press release, “Our customers told us that the pain, inconvenience and indiscretion of finger pricking were the key reasons they weren't managing their diabetes as well as they should. Addressing these concerns has guided the development of FreeStyle Libre – a transformational product designed to not only remove the pain of finger pricking but also seamlessly integrate into their daily lives.” Assuming pricing and reimbursement work out, we share Mr. Ford’s enthusiasm over this product’s potential –the majority of people with diabetes are not at their target glucose levels, and yet, more frequent glucose monitoring has the potential to help patients improve their diabetes management. To date, however, testing more frequently has meant more pain, less discretion, more hassle, and lots of confusion in interpreting the data. FreeStyle Libre hits these unmet needs in its product design, and we look forward to seeing its uptake in the marketplace.
• Cost and reimbursement will be critical factors in this product’s success; the company has yet to provide details on either of these fronts. However, management did confirm the product will be priced “significantly less” than CGM and a “bit more” than BGM. If that is correct (a “bit more”) we would anticipate there would be a major market for it. Management also acknowledged Abbott’s intention of working with European reimbursement authorities to secure reimbursement and will utilize the findings of clinical trials, such as REPLACE, for this purpose. The company presumably plans to show significant clinical benefit to obtain reimbursement that is preferable to BGM.
  
  • To date, payers in Europe have made access to CGM very challenging, which stems from the high current cost of CGM combined with only moderate clinical efficacy. Results to date have shown an overall A1c reduction ~0.5% in many studies; this is incredibly frustrating of course, since CGM reduces hypoglycemia for most people – which narrows the A1c drop – and increases time in zone. We expect that Abbott will show stronger clinical efficacy through use of the entire system – the real-time component and the Ambulatory Glucose Profile download.
• We expect the initial launch of Freestyle Libre to focus on all insulin users, especially on MDIs whether they are type 1 or type 2. We believe that the device could be very attractive for patients who are looking for a low-hassle and discrete option for obtaining more complete glucose information. Other likely candidates for this product include intensively managed patients and their HCPs that have not embraced CGM (for whatever reason – cost, the need for fingersticks, inaccuracy, perceived hassle factor regarding alarms, etc.). Certainly, CGM has low enough penetration (~9% in the US T1D Exchange [per Dr. Irl Hirsch’s talk at AADE 2014], and much lower penetration abroad) that there is plenty of room to grow, even if a number of people turn to this new alternative. We also believe that those most drawn to this will be those that haven’t turned to CGM and aren’t really CGM candidates:
  
  • Type 2 patients who need to monitor diabetes closely when making therapeutic changes
  • People who can’t afford CGM
  • Pregnant patients
  • Elderly patients (while this is a challenging group, we can see this being especially appreciated by children of elderly patients – “Mom! Can you scan your glucose for me!”)
  • Children with type 1 diabetes (where frequent glucose monitoring is challenging)
  • Inpatients
  • People with prediabetes and at high risk of “converting” to type 2 diabetes (this is probably a group for which it will be challenging to gain reimbursement; on the other hand, if we want to work on prevention as a country – this should be an easy way for people with pre-diabetes to monitor process)
  • People who are at high risk of type 1 diabetes but do not want to use traditional blood glucose monitoring
• FreeStyle Libre has already demonstrated strong preliminary accuracy in studies presented at the aforementioned three conferences (EASD 2013, DTM 2013, ATTD 2014). We are optimistic that the CE Mark data, which is to be presented during the Abbott Symposium at EASD 2014, will be largely consistent with that discussed below and previous studies of the FreeStyle Navigator sensor.
  
  • ATTD 2014: A six-lot calibration study enrolled six patients with diabetes that each wore three sensors simultaneously over five days. Overall MARD (vs. FreeStyle Precision fingersticks) using a lot-specific pre-determined (prospective) factory calibration was a solid 11%, with 84% of points in Zone A of the Parkes consensus error grid.
  • EASD 2013: Abbott’s first feasibility study (n=12) of the FreeStyle Libre demonstrated impressive accuracy in patients with type 1 diabetes over 14 days – MARD was 8.5% vs. YSI (n=1,582) and 9.6% vs. FreeStyle Lite fingersticks (n=882). A solid 91% of values (vs. YSI) and 93% of values (vs. FreeStyle Lite) fell in Zone A of the Parkes Consensus Error Grid.
  • DTM 2013: An outpatient clinical study of 62 patients (50 with type 1 diabetes + 12 with type 2 diabetes) demonstrated that factory calibration is a feasible option and can produce comparable accuracy compared to fingerstick calibration. The study showed that the 14-day sensor’s MARD was 13.9% using the five-day FreeStyle Navigator algorithm (extended by adding one calibration every two days; 10 calibrations per 14 days), similar to a MARD of 14.0% using a simulated factory calibration applied over the whole 14-day sensor wear period. An important note – this study used different hardware and algorithms than the other studies mentioned here.
• A trial posted on ClinicalTrials.gov (Identifier: NCT02082184) is evaluating FreeStyle Libre in patients with type 2 diabetes. The study, An Evaluation of a Novel Glucose Sensing Technology in Type 2 Diabetes (REPLACE – aptly titled!) is a randomized, parallel assignment study evaluating the impact of the FreeStyle Libre on A1c vs. self-monitoring blood glucose (with an Abbott meter) in patients with type 2 diabetes using insulin. The primary endpoint of the study is A1c at six months, and the estimated enrollment is 210, with a primary completion date slated for November 2014 – we would expect to see results at ATTD 2015. The trial is currently recruiting patients in 26 locations in the UK, Germany, and France – regrettably (and predictably) this study is restricted to the EU.
• In Abbott’s 2Q14 call, management commented that the FreeStyle Libre will be followed by other versions of the product for various segments of the market. We expect future iterations to be targeted more specifically at type 1 patients. Bigger picture, we could see Flash Glucose Monitoring being popular among all patients needing help with identifying glucose patterns and medication titration; we do think many type 1s rely on CGM alarms and would not want to change to FreeStyle Libre – we can, scarily, think of some type A type 1s who would want both (CGM for alarms, Flash Libre for the rest of monitoring).
• Also in the 2Q14 call, management remarked in Q&A that FreeStyle Libre “will come to the US and will be a global product.” We assume the regulatory challenges here in the US will concern obtaining an insulin-dosing claim for the product. During Dexcom’s 2Q14 financial update, we heard that the company is working with the FDA to obtain an insulin-dosing claim for the G4 Platinum. Management said that the “accuracy, consistency, and performance is there” based on the G4AP data shared at ADA 2014 (MARD of 9.0% vs. YSI in 51 patients vs. fingerstick MARD of 5% vs. YSI). Dexcom has started putting together the information and risk mitigation strategies, and management indicated it will proceed with this label update on the current G4 Platinum system.
• Abbott has created a new category with Flash Glucose Monitoring, something that has proven wildly successful in many other consumer domains. In short, Flash Glucose Monitoring is fundamentally trying to take something that is more “professional” (i.e., traditional CGM) and make it more accessible to the masses. In consumer packaged goods, examples of this strategy include home espresso makers (e.g., Keurig), cleaning products (e.g., dilutable floor cleaners, spray cleaners, wipes, toilet wands), and teeth whitening (e.g., whitening strips). In these cases, the new innovation completely changed the entire category; we look forward to seeing if Flash Glucose Monitoring does something similar in diabetes.

Image of FreeStyle Libre

Close Concerns Questions

Q: How will the device be priced?

Q: In which of the seven European countries will FreeStyle Libre launch first?

Q: Will FreeStyle Libre be launched with reimbursement? Is it going to be similar to Navigator reimbursement?

Q: Is the device only approved for upper arm wear?

Q: How was the CE Mark study designed? Was it 14 days with YSI in-clinic days spaced throughout?

Q: What was the overall MARD that will be included in the label?

Q: Is the software Mac and PC compatible?

Q: When will FreeStyle Libre be submitted in the US?

-- by Adam Brown, Varun Iyengar, and Kelly Close