Lilly Diabetes Blogger Summit 2018 at the Cambridge Innovation Center

May 3-4, 2018; Cambridge, MA; Highlights - Draft

Executive Highlights

  • CTO Mr. Matt Clemente, with some help from VP Ms. Marie Schiller, proudly showed off Lilly’s in-development hybrid closed loop, featuring a tiny disc-shaped tubed pump with no screen, an app/wireless controller with the user interface, and Dexcom’s G6 CGM. He also discussed, but did not show, the Integrated Insulin Management system, which includes dose capture for disposable insulin pens, a dose titration app, and glucose monitoring devices. While the hybrid closed loop will definitely roll out with Dexcom G6 integration at launch, the Integrated Insulin Management system's integration with Dexcom is still in the development stage and no guidance on launch date was given. The guidance for a market entry in two-to-three years for both systems was maintained – from the November debut, that puts launch in late 2019-2020. 

  • We weren’t allowed to take pictures, but Lilly’s pump was significantly smaller and slimmer than we expected. It was about ~two inches in diameter and a ~half-inch thick, and we heard people compare the shape to that of a tape measure or a shuffleboard puck (obscure, but very accurate) – this was more accurate than the “shoe-polish tin” description we heard last November. The pump holds 100-300 units of insulin in a disposable reservoir that fits into a reusable, rechargeable-battery-powered pumping mechanism. Similar to Bigfoot, Lilly has gone with no user interface or screen on the pump – it has just one button for manual on-demand boluses, and will otherwise be controlled by a wireless handheld and/or a smartphone app (depending on regulatory progress). Like Tandem’s t:sport, the vision is flexible wear – the disc-shaped pump can be worn adhered to the body with a short luer lock infusion set (like a patch) or in the pocket with a longer infusion set (like a traditional pump). The MPC algorithm licensed from Montreal AP is embedded on the pump, talks directly to the G6, and will keep someone in hybrid closed loop even when the handheld is out of range (similar to Omnipod Horizon). Affordability is a guiding principle in the design, and we’d have to assume Lilly could bundle insulin into the complete system pricing. Notably, the app strongly resembles and includes familiar user interface/display as Dexcom’s G5/G6 apps.

  • The Integrated Insulin Management system will leverage dose capture devices that fit onto the disposable KwikPen, CGM/BGM/FreeStyle Libre, and other sensors. Management wouldn’t specify the form of the dose capture devices (i.e., how it fits on the pen – Sleeve? Cap? Dial?). The Lilly team is intent on having this system integrate seamlessly with provider workflow, and Ms. Schiller hinted that there is a lot of insight yet to be tapped from BGM and professional CGM – nice! Assuming the cost comes down, it sounded like a fully disposable, smart KwikPen could come in the pipeline.

  • Overall, today showed that Lilly’s automated insulin delivery and digital health efforts are meaningful, consumer-grade, and quite far along. With this center, the pharma giant has co-located software, hardware, and drug formulation; provided ample funding; and allowed the ~40-person Cambridge team to be agile and innovative. As Dr. Howard Wolpert said, “It’s only in an environment like this where one has the resources and expertise. It requires a lot of iteration, and it also requires a lot of funding. It’s only something that one could accomplish at a place like this.”

Greetings from Cambridge, MA, where earlier today, Brian and Adam were two of the first 12 members of the public to hold Lilly’s new, Dean Kamen-designed insulin pump. The opportunity came as a perk of attending a small Summit to learn all about Lilly’s Connected Care vision from the company’s leaders, including VPs Dr. Howard Wolpert and Ms. Marie Schiller. The day included a quick tour around the three-year-old Cambridge Innovation Center, an interactive panel discussion, and best of all, a “show and tell” with CTO Mr. Matt Clemente on the in-development hybrid closed loop system and “Integrated Insulin Management” system (smart pen with MDI dose titration). Mr. Clemente was excited to be showing off the automated systems to people not involved with the project for the first time after “obsessing” over them for three years. Read on for the details we gleaned about both systems!

First, some background on what we knew coming in to the day: The Wall Street Journal broke the news of Lilly’s massive effort in digital/tech back in November (see our extensive coverage). The company intends to launch both systems (AID and Integrated Insulin Management), over the next two-to-three years (putting launches somewhere between November 2019-November 2020). A non-exclusive development agreement was signed with Dexcom to bring its CGM into the first clinical trials with both systems. The first phase 1 safety/functionality study of the AID system (n=30), which began in mid-December, wrapped up in February (no results have been shared). Finally, Lilly partnered with Rimidi, also in December, to develop provider-focused tools for the integrated insulin management system.

**Any prototype products detailed below are in-development and not approved for use. This event was paid for and sponsored by Lilly Diabetes.

Hybrid Closed Loop Show and Tell

Lilly’s hybrid closed loop system is still slated to launch in two-to-three years, notably, with Dexcom’s G6 iCGM at launch (the company had previously shared that Dexcom was a development partner, but not that they would be commercial partners, nor that G6 would be used, rather than G5). Lilly likely won’t be the first hybrid closed loop system to the US market with G6 integration (Tandem expects a US launch of its G6-integrated hybrid closed loop in 1H19), but going straight to G6 is the obvious move given the lower class iCGM pathway and Lilly’s timing. We were unfortunately not permitted to take pictures of the custom, Dean Kamen-designed pump, but Lilly’s prior description of it as a “white disk about the size of a shoe-polish tin” was modest – it’s actually smaller than that (see more details below). The pump holds the control algorithm, licensed from Montreal-based Class AP (tested in Dr. Ahmad Haidar’s McGill group). Dr. Haidar will join the Summit tomorrow, so we look forward to learning more about the algorithm then, especially automatic correction boluses, adjustable set points, initialization needs, adaptation, etc. The first phase 1 study of this system began in December and wrapped up in February, but results haven’t yet been posted. All in all, Lilly presented a system that is a lot further along in development than we expected, including G6 integration and app display built directly into Lilly’s app. The company brings an ambitious vision of flexibility and usability to the table.

Pump Details and Impressions

Form factor

  • We would ballpark the diameter of the pump at ~two inches, and the height at ~half-an-inch – it fits very comfortably in the palm of the average hand and is significantly smaller than we had envisioned

  • We heard the following comparisons for shape/size: Small measuring tape; shuffleboard puck

  • The disk had ~three inches of tubing emerging from the top

Reservoir

  • The unique flexible reservoir (described by Adam as an “elastomeric bladder”) holds a maximum of three mL of insulin (between 100-300 units); ~three days of insulin

  • At launch, patients will self-fill the reservoir with whatever insulin they please/can access, though pre-filled reservoirs are in the pipeline

  • The disposable reservoir can be accessed by screwing the top half of the pump off the bottom (similar to taking a drug cap off the bottle)

On-pump features

  • The pump does not have a screen or a user interface or navigation buttons –interaction with the system will happen on the phone/wireless controller.

  • The pump embeds the control algorithm (see below) and talks directly to G6

  • There is a single, oblong button on the side of the disk near where the tubing emerges – it administers manual boluses when pressed.

    • It was not clear whether users could pre-program the size of a bolus administered when they press the button (e.g., 0.25 units, 1 unit, …). Further work is underway to ensure that patients don’t accidentally trigger a bolus or deliver too much insulin by accident (i.e., forget how big the bolus is programmed for)

    •  

Algorithm

  • The MPC algorithm licensed from Montreal AP is embedded on the pump, so no controller/phone has to be around for the system to run

  • Lilly has also licensed Class AP's dual hormone algorithm (insulin+glucagon), though this will not be included in the first generation system

Remote control

  • Lilly is developing both wireless dedicated handheld controllers and apps for iOS and Android phones – since the pump has no user interface, this is how users will monitor and interact with their systems. The concept is identical to what Bigfoot is doing with its tubed system.

  • From a technological standpoint, Mr. Clemente sees no limitation to having both the app and the dedicated controller ready at launch; however, there are a lot of “what-ifs” on the regulatory side for dosing from a phone.

    • Ms. Schiller emphasized that Lilly doesn’t want the perfect to be the enemy of the good, implying that a dedicated handheld may be required at launch

  • Read more about the app below

Durable/Consumable components

  • The pumpable mechanism is durable and would last “more than a year” (management wouldn’t comment on whether it could last up to four years), while the flexible reservoirs and fluid path is disposable. This type of modular design is expected to save cost.

  • The disposable reservoir piece was very, very slim, meaning most of the pump volume is electronics. We imagine with further electronics refinement, the disc-shaped pump could get even smaller.

Wear modalities

  • At launch the pump will be able to be used in two ways:

    • (i) Worn as a patch with a short infusion set

    • (ii) Worn in the pocket (i.e., like a conventional tubed pump) with a longer infusion set.

  • A tubeless patch pump form factor will not be available at launch, but will “eventually probably” launch

  • We love this flexibility!

Infusion set connector

  • The tubing’s connector is Luer Lock-compatible (currently the only company that has shared plans to support this connector on the US market, barring a Roche re-entry)

  • Management was vague about plans to develop infusion sets, though Ms. Schiller enthusiastically commented, “If it’s a problem, we want to fix it!”

Insulin delivery sensing

  • Lilly’s pump measures “every little micro-dose of insulin that’s delivered” and feeds that data back into the closed loop algorithm.

  • We’re not sure how the marginal cost of this feature compares to its marginal benefit. On the one hand, it is smart to carefully track and confirm insulin delivery, but on the other hand, the body’s use of insulin is such a fickle black box, that reducing the uncertainty of one variable (insulin delivered) may not have a huge impact – insulin must still behave consistently once it makes it into the body, which is impossible given that there are at least 42 factors that influence blood glucose. That said, if the price is right, this input can only help.

Pumping mechanism

  • Mr. Clemente was intentionally vague, but insulin is ejected using small pump chambers and a series of valves driving delivery

Batteries

  • The pump is battery-powered, with each re-chargeable battery currently intended to last three days. The pump will come with multiple batteries so that while one is being re-charged, the other is in use.

  • Three-day battery life is convenient, as it aligns with set and reservoir changes.

Pricing

  • No financial specifics were provided, though the pump’s durable/disposable design leaves potential for a traditional model (e.g., Medtronic, Tandem) and more of a subscription/recurring revenue/bundled model (e.g., Insulet, Bigfoot).

Companion App Resembles and Leverages Dexcom’s Mobile Software

We were given an abbreviated tour of the prototype companion app, which strongly resembled Dexcom’s G5/G6 mobile apps. According to Lilly’s team, this was no accident – they worked very closely with Dexcom to integrate the latter’s software libraries. “There’s no need to fix things if they aren’t broken, and there’s no need for people to learn a new interface.” Indeed, Lilly’s app shows the user’s current glucose levels in a circle in the top half of the screen, with a trend arrow jutting out of the side of the circle – the visual display is identical to the G5 app. Below the current glucose reading is the Dexcom mobile historical glucose data chart with dots representing glucose every five minutes. When turned in landscape, insulin delivery curves are displayed below the glucose levels. The app connects to CGM, BGM, the cloud, the pump, and can sync with other devices like activity trackers. Other features we noticed: The user can easily toggle in and out of “auto mode” (but Mr. Clemente notes users will seldom be kicked out by the system, barring connectivity issues), administer a remote bolus, and input food intake. Unfortunately, we didn’t get to play with the app ourselves or pick up on other features, but we were very impressed by its very commercial feel – everything seemed very logically laid-out and easy to navigate.

  •  Mr. Clemente and Ms. Schiller foreshadowed a vision in which customers might switch between closed loop and Integrated Insulin Management at will since the data will all be stored in a common pool. This is a very compelling proposition – many pumpers have at one time or another tired of infusion sets and having a device tethered to them, so they switch back to MDI. With this vision, the data would still be captured and the patient would still have automated dosing guidance. The question is, would payers pay for individuals to have both systems at the same time? Could this really be made seamless? Could this level of flexibility lead to even better outcomes?

  • Patients can use both the G6 Mobile app and Lilly’s app side-by-side if desired, but Lilly’s app will receive the CGM signal directly and incorporate other features. It’s great to see Lilly thinking about small but important nuances like this – running two apps adds burden. This also shows how closely Dexcom and Lilly are working together.   

Integrated Insulin Management Show and Tell

The Integrated Insulin Management system consists of a dosage guidance app that leverages connected dose capture devices compatible with Lilly’s disposable KwikPen, CGM, BGM, FGM, and other sensors (e.g., exercise). It is also slated to launch in the next two-to-three years. It was not shown today. When we asked about the form of the dose capture device(s) in-development – “Cap? Dial? Sleeve?” – Ms. Schiller joked, “all of the above or choose one of those.” We were also later told that a connected, disposable KwikPen is under development. Whatever the shape and mechanism, management confirmed that the user interface exists solely on the app, with no buttons or screens on the device itself. The decision to focus on disposable pens was clearly intentional – this approach has a lot of upside as it doesn’t change the way in which patients obtain their pens, they won’t have to re-train on new pens, and many patients appreciate being able to use and subsequently discard. Lilly’s investment in Companion Medical was mentioned, positioning the InPen as a reusable smart pen option that is different from what Lilly will offer with the disposable KwikPen platform. We have not heard launch metrics for Companion’s InPen, but we tend to agree that the disposable route is easier for prescribing and use – assuming the attachment works.

  • Lilly is working with “multiple partners” for CGM, but will launch with Dexcom at first. Ms. Schiller also conjectured that there is a lot more value to be derived from BGM or professional CGM/FreeStyle Libre. Yes! Not every patient will want to use CGM – figuring out how to get the most out of BGM and/or professional CGM is an area that we’re very hopeful for in the next couple of years.

  • Ms. Schiller said that Lilly is “focused on staying in the healthcare provider workflow”; a doctor could see that an individual is on insulin and then receive a reminder to offer Lilly’s titration tool with the next prescription. She stressed that this would have to be a seamless process, which could prove difficult since EMRs are so unique from clinic to clinic. This language sounded like a potential sandbox for Lilly’s Rimidi partnership – Rimidi’s software will integrate into clinicians’ workflows on top of electronic medical records (EMRs), providing therapeutic guidance and identifying optimal treatment plans.

  • Lilly is currently recruiting for a smart pen study investigating the frequency and effect of missed meal boluses (n=68; blinded and un-blinded CGM). We imagine this study is related to Lilly’s Connected Care, but the company hasn’t spoken about it or how it plays into their larger plans.

Lilly Connected Care Leadership Panel – Quotable Quotes

  • “We’re at a junction where diabetes care can be completely transformed with tech. Look at devices, mobile phones, cloud computing – I think the opportunity is there. It’s only in an environment like this where one has the resources and expertise. It requires a lot of iteration, and it also requires a lot of funding. It’s only something that one could accomplish at a place like this.” – Dr. Howard Wolpert (VP, Medical Innovation)

  • “The burden of data. What’s striking in the past 25 years, post-DCCT, we’ve recognized that we can improve outcomes, and the entire interaction has been around numbers. When diaTribe asked me what I thought a time-in-range goal should be, I qualified my answer. My concern about focusing on numbers is we’re basically setting people up for failure. Most goals we give are frankly unachievable. And most people don’t have a perspective. What’s the risk of blindness in people with retinopathy? Less than 1%. And less than 50% of people with type 1 get proliferative retinopathy. The risk of complications is extremely low.” – Dr. Wolpert

  • “How can I ensure you will have access [to these systems]? I can prove there’s a reason why the insurance company should allow you to have the product. That’s the importance of outcomes. We must show the product is not a nice-to-have, but imperative to ensuring the outcomes, including cost, that we want. Our hope is if we show outcomes, we can improve outcomes. How do you prove outcomes? Is that in RCTs? Maybe that doesn’t reflect the real world. So you have to be willing to open up your data. You have to be confident enough that your technology will improve outcomes or we shouldn’t be doing what we’re doing.” – Ms. Marie Schiller (VP, Connected Care)

  • “We’re partnering with some behavioral researchers, implementing survey instruments identifying social determinants of health. The opportunity with tools here is to identify what specific barriers and challenges people are facing in their lives. As a clinician, I think what’s the barrier, and what do I need to do to engage a patient? Another focus of this initiative is to provide guidance for clinicians on how to discuss these issues. A big concern with connected device data is that it would be used to bludgeon and blame patients, which is obviously totally counterproductive. If one doesn’t present data in a way that’s dispassionate and non-judgmental, then it will end up counterproductive.” – Dr. Wolpert

 

-- by Brian Levine, Adam Brown, and Kelly Close