Medtronic. Dexcom. Abbott. Sanofi. Google. A lot of very large, well-known companies are investing heavily into innovating the diabetes space, and that innovation is exciting. But a disproportionate amount of the innovation around insulin delivery focuses on the insulin pump, a delivery device that’s only used by a small percentage of insulin users. Most insulin users — between 70 and 93 percent, depending on whose figures you use and what part of the world you’re looking at — use an insulin pen, a device developed by Novo Nordisk in the eighties and relatively unchanged since then.

A small crop of startups has decided that it’s high time connected health innovation came to the insulin pen. One of the leaders of the pack — a San Diego startup called Companion Medical — is led by a veteran of those big company efforts. CEO Sean Saint previously worked at Medtronic, Dexcom, and Tandem Diabetes.

“Here I am at Tandem asking this question ‘How do we get more people to use the insulin pump?’” he told MobiHealthNews. “And that’s the right question for Tandem. So we’re asking questions like 'Why will you or won’t you use an insulin pump?' and we’re getting answers like tubing, cost, complexity that sort of thing. To be frank I was getting a little frustrated with the patient, and asking ‘Why won’t you use this great technology we’re developing?’” 

That’s when Saint found himself on the other side of the pump: He was diagnosed with Type 1 diabetes.

“For me it caused me to look in the mirror and say ‘Stop being frustrated with people who won’t use your great technology. They have their reasons.’ Instead, let’s ask a different question. Let’s ask ‘How do we bring the benefits of insulin pumps to the 93 percent of people who use insulin who are pen and syringe users?’”

Companion Medical, with backing from Eli Lilly and Company, announced this past summer that it had FDA clearance to do just that. And in the months that followed, three other companies came out of stealth announcing that they were working on similar offerings. A fifth, Emperra, has been quietly developing its own smart insulin pen in Germany and will soon be ready to take it to other parts of the world. 

First Patients Pending, a London company that had already innovated the insulin pen space with a non-connected cap called Timesulin, announced that it was working on a smartphone-connected product. Then an Irish group called Innovation Zed, which also had a pre-existing nonconnected insulin pen accessory, announced its plans to enter the space. And finally a second US company, Cambridge, Massachusetts-based Common Sensing, announced a trial funded by Sanofi and led by the Joslin Diabetes Center.

What all these companies have in common is they recognize that, though it might be the focus of big companies, the insulin pump is not the preferred device of the masses.

“We’ve talked to a lot of people in the space and what we’ve learned is that, first of all, not everyone prefers pumps,” James White, president of Common Sensing, told MobiHealthNews. “There’s people that have access to them and a lot of them choose not to use pumps. There’s people who want access and can’t get them. But we’re pretty sure for the next five to 10 years there is not a pump both for the market and everyone’s preferences, so there won’t be that 'coming together' to take any kind of authority in the market. We talk with pharma companies and we hear a fair amount of their predictions. And as nice as the pump is for some people, for a lot of people it just doesn’t make sense.”

Creating a connected insulin pen is a leap of several steps at a time. Unlike, say, fingerstick glucometers, which have always collected data but didn’t always store or transmit it, the traditional insulin pen doesn’t collect data at all. If patients want a record of how much insulin they used, they have to eyeball it and write it down. A connected pen is first and foremost an adherence play, but it can go much further — by interfacing with glucometer or CGM data or self-reported food data, a connected insulin pen could allow pen users to live some variant of the artificial pancreas dream, which up until now has only been a possibility for pump users.

“I believe that the insulin data is the most important data that we have,” Patients Pending CEO and cofounder John Sjölund told MobiHealthNews. “Currently, every time you turn the dial and inject yourself, it just disappears. All of the blood sugar and especially the CGMs, they exist, they’re good enough and the apps exist and they’re getting better. But the insulin information is just missing. And that’s the piece of the pie we bring out, and what’s important is the accuracy we bring to the table.”

From insulin adherence to insulin management

One way in which the various companies in this space differ is exactly what problem they’re using connectivity to solve. For most of the startups right now, the objective is simply to collect the data of how a often a patient uses an insulin pen and how much insulin they inject, and to use that data to drive adherence.

“The [device] we announced this week is the first step, we’re tackling that 60 to 70 percent adherence rate of insulin users,” John Hughes, CEO of Innovation Zed, told MobiHealthNews. “The insulin user audience are at a very low level of compliance. You show up at the doctor and inevitably when you get there, you don’t have your records. They’re working on anecdotal data. We have focus groups [of doctors] that we work with and they tell us, they cannot trust the data that they’re getting.”

The most basic advantage of tracking pen usage doesn’t require connectivity at all. Patients Pending’s original product, Timesulin, is a cap for insulin pens that starts a timer when it’s removed and replaced, so that patients can always look at it and see when their most recent dose was. Even this is useful information that can help prevent double dosing. 

Adding connectivity also allows a device to send alerts about a missed dose to the patient’s smartphone, or to alert a patient’s physician, caregiver, or coach when they miss a dose. That’s where James White, president of Common Sensing, sees the initial value of the technology.

“Right now, people go home from the doctor after being given insulin for the first time and they don’t have another touchpoint for three months with anything,” he told MobiHealthNews. “Their data is theirs, they’re looking at it, they often don’t know how to interpret it because they weren’t taught at the doctor, and more than half of those people, in those first three months, drop off. They come back and they’re not using it. They haven’t filled all their prescriptions, things like that. The reasons vary a ton. Sometimes people aren’t prescribed needles to use with their insulin pen. Some people don’t know how to use it, they’re afraid to inject something new, or they don’t remember the instructions.”

Common Sensing's Gocap is focused on collecting the data and sending it to a smartphone app, from whence it can also be sent to a data aggregator or a caregiver. The company is looking into developing its device for different levels of tech savvy: some use cases might allow for more patient engagement while others are designed to be more passive.

“We’ve sent this home now with a fair number of people and we’ve seen a wide spectrum. Some people don’t have a smartphone, they want to keep a very cheap mobile data device plugged into the wall and never look at it and use this hardware device. They know the data’s going somewhere, to their doctor, and that’s all they care about,” he said. “And then some people are the power users, just like any product. They want to get into the data, enable that exact setting, see every new dose they’ve done, understand the accuracy and the glucose readings.”

As an adherence play, the space is very reminiscent of another medication delivery device that’s recently blossomed into a burgeoning industry in digital health: the connected, sensor-laden inhaler. After some early success by companies like Propeller Health, the connected inhaler space rapidly became a hot acquisition target for the pharmaceutical industry. The comparison isn’t lost on insulin pen innovators. 

“What I like about insulin and why we made it a first target for the company is that right now, you know, inhalers can be expensive when they’re taken incorrectly, but the cost burden on the healthcare system right now of incorrect insulin use is far greater than any other medication,” White said. “Pharma right now loses on the order of a third of revenue they could be getting just because a third of prescriptions are never picked up. And not only that but among people who are using it it’s not being used very effectively. So a company that can differentiate in making their insulin more effective stands to benefit, and that’s why companies like Sanofi are interested.”

So far at least two major pharma companies have invested in this space: Sanofi has invested in Common Sensing and Lilly has invested in Companion Medical. Neither of those investments has “strings attached” according to the two companies, but the interest is certainly notable. 

But Sean Saint, of Companion, sees the insulin pen space as being much deeper than the inhaler space. 

“The connected inhaler market is a compliance tool,” he said. “And that’s wonderful, because we all know about compliance problems. And we have 100 percent of that benefit. Same exact thing. But one of the biggest problems in diabetes is not that I don't remember to take my dose, but how much do I take? I know my blood sugar, I know what I have recently eaten and my recent insulin doses, so how much insulin do I take right now? That’s what a dose calculator provides and we are the only company I am aware of in the connected pen/cap space that has a dose calculator and certainly the only one cleared by FDA.”

That’s why Companion Medical has FDA 510(k) clearance while some of the other companies are holding off. (Common Sensing is registered with the FDA but White doesn’t believe it’s current adherence-focused offering requires premarket approval). By taking the next step and offering a dose calculator, and starting to offer advice on how much insulin a patient could take, the company enters a new risk category, but also potentially offers even more benefits to people with diabetes. 

Saint's company’s goal is to create a learning dose calculator, which will use the same kind of algorithms closed-loop “artificial pancreas” systems use, but with a connected pen rather than a pump as the delivery method.

“You can call it a poor man’s artificial pancreas or artificial pancreas light or whatever you want to call it, but it’s basically using the same algorithms and applying them to mobile injection therapy,” he said. “Nobody’s ever done that, so nobody knows what the ultimate clinical benefit of that will be, but we know that there will be one.”

For Patients Pending and Common Sensing, that functionality could be in the cards eventually, but they don’t see a reason to reinvent the wheel. Once the data is accurately collected and sent to a smartphone, third party apps can focus on making it actionable for the user. 

“We’ve had a lot of experience developing software, but we’ve also learned how tricky healthcare and medical apps is,” Patients Pending’s Sjölund said. “And there are a lot of apps in the space already.”

Pens, caps, and wraps

Another differentiating factor between the various companies is the form factor. Only two of the five companies make a full-on insulin pen, two make smart pen caps, and one, Innovation Zed, makes a unique wraparound device that fits on the back part of the pen.

There are different facets to the decision. One is that, most companies agree, creating an entire insulin pen is a more daunting endeavor than creating an add-on.

“At first we thought, hey let’s build a digital pen,” Innovation Zed’s John Hughes told MobiHealthNews. “Not being very experienced in medical device market we were quickly put off by the regulatory implications of such a device. We thought, it will take us seven years to do that. So we came up with the concept of an add-on technology.”

Saint, at Companion, echoed these sentiments, though his company did decide to go down the full pen road (as did Emperra in Germany).

“One thing I can absolutely assure you: we did not design a full insulin pen instead of a cap because we thought it would be fun,” he said. “We considered the different solutions and we decided that the only way we could provide a solution to the patient that was going to be truly transparent to their current therapy was to control the whole experience. And that’s why we went with the pen.”

Controlling the whole device simplifies the design of the sensors and allows Companion Medical to include a larger battery — their device will last a year with no need to plug in or replace batteries, compared to Common Sensing’s cap, which will have to be plugged in once a week (though White says they’re also working on a version with a longer-term battery). It also allows for some complex features, like compensating for inaccuracies that can be caused by priming the pen (activating it without dosing to eliminate air bubbles).

On the other hand, add-on solutions have some added convenience in the market. While Companion’s device will replace a durable pen, other devices can work with disposable insulin pens, which are currently more popular. 

“We diabetics are a pretty conservative lot and we don’t like changing our habits,” Innovation Zed’s Hughes said. “So when we get used to insulin pens we want to keep them. So we offer them a sleeve that wraps around the pen and a timer devices that clips on to the sleeve and is triggered only when the injection is completed.”

Saint thinks the additional value will be enough to persuade patients to change their habits. Caps are also likely cheaper to produce, but that could be a moot point if health insurers start routinely reimbursing for the devices.

The path to market and reimbursement

Although the space is just starting to emerge into public consciousness, the players have been working quietly on it for years, and now the race to market is on.

One company, Emperra, has a big lead, but it has only focused on its native Germany. It’s CE-marked Esysta pen is already on the market in Germany and reimbursable by German payers.

“We are on the market,” Emperra CEO Christian Krey told MobiHealthNews in an email. “It is working and has proved success. We are reimbursed by all health insurers in Germany. We have a unique software, that connects patients, relatives, nurses and physicians with high secured servers. We have unique contracts with health insurers that pay not only for the hardware, but also for data sharing between patient and the physician as well as for coaching the patients, depending on their needs.”

He also said the company has “proven success in a field trial together with a health insurer, that the use of the ESYSTA system leads to significant lowering of HbA1c without more usage of insulin.”

Emperra is already making inroads in the rest of the EU and in the US. The company has filed for FDA approval and hopes to enter the US market next year.

Innovation Zed also has trial data showing its product improves HbA1c, thanks to a partnership with the UK’s NHS. The Irish company also has a joint venture with Swedish injectables manufacturer SHL Group that could help them bring their new solution to market quickly once it’s fully developed. They’re targeting a 2017 European launch for the connected product and eyeing the US shortly thereafter. They are hoping for reimbursement from national systems like the NHS and from private payers in the US.

Common Sensing recently announced a clinical trial with Joslin Diabetes Center. Their product is ready to go, White says. 

“The device is ready now, so what we’re looking for is the most efficient way to commercialize it with those services to insurers, self-insured employers, etc.,” he said. 

Similarly, Companion Medical’s Sean Saint says his company is planning for commercialization in 2017, having been focused up until now on the FDA clearance.

“Smart pens are not a category yet,” he said. “We have the first cleared smart pen, and we’re going to be in the unenviable position of starting to figure out pricing on that. Pricing what amounts to a new category of devices can be very challenging. On the one hand, we have the negative that we look a lot like a traditional insulin pen. On the other hand we have the positive that we believe we offer a very significant clinical benefit over and above traditional insulin pens and potentially as much as a pump. So certainly the pricing will be in between traditional insulin pens and pumps. But I can’t tell you exactly where at this point.”

He says there will be some work to do for reimbursement, but he’s confident that the device will eventually be covered via the pharmacy benefit of a prescription drug plan. White agrees that reimbursement is inevitable.

“The general idea is we don’t want people to have to pay for this out of pocket,” he said. “The idea that patients are causing the problem right now is one that shouldn’t really exist in any modern society. And that means that patients shouldn’t be responsible for fixing this problem in terms of paying for their own medicine. So in our minds, the people who stand to gain the most from this are insurance companies and pharma companies. If someone switches from taking their insulin to not taking their insulin, in the next year they will probably cost on the order of $2,500 more per year and the insurer’s paying for all of that.”

Innovation in the diabetes space is coming in a lot of forms from a lot of places, from the artificial pancreas, to AI coaching, to glucose-sensing contact lenses. But when it comes to making a big difference right now in the lives of many insulin-using type 1 diabetics, smart pens might just be the next big thing. As Saint pointed out, the market is so much larger for pens that even a modest improvement in diabetes management could help a lot of people.

"The health economics of smart pens are phenomenal when you start to think about them," he said.