The Promise of Smart Glucagon: No More Living in Fear of Hypos

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Most people who follow developments in the diabetes world have probably heard about efforts to create smart insulin, which would sense when blood glucose levels are rising and respond accordingly. But what about the flip side of the coin, something that could respond when glucose levels are falling precipitously? Protomer Technologies, a biotechnology company based in Pasadena, California, is already working on developing smart insulin. Now they’re in the early stages of working on smart glucagon, which would quietly circulate in the body until activated by low glucose levels. In the spring, Protomer’s concept won the T1D Exchange’s Diabetes Innovation Challenge, a competition to “identify, nurture and fast-track innovative scientific and clinical solutions for diabetes.” (The competition drew sixty entries from around the world; other finalists included a company developing smart insoles that would help predict foot ulcers, and a bandage-thin “patch pump” that could dispense insulin along with other medications.)

Alborz Mahdavi, Protomer’s founder and CEO, told me that his company decided to focus on smart glucagon for a couple of reasons: they felt that they had the right background and technical experience to tackle the problem, and they saw an important unmet need. In its current form, glucagon is a powder that must first be mixed with a sterile solution and then injected. If someone is alone and experiencing hypoglycemia severe enough to require glucagon, they’re very unlikely to be able to formulate the glucagon themselves. This means they must be lucky enough to have someone there who knows how to formulate it and inject it.  Smart glucagon, however, would activate within the body when—and only when—needed. Mahdavi points out that few companies are working in this space, partly because the glucagon market is tiny compared to the insulin market. “But honestly, money issues aside, we just thought about it and said, if this thing was available now, what kind of impact would it have? It’s going to be huge. There are people who are dying, twenty and thirty year olds, dying from hypoglycemia. They go to sleep, have a hypoglycemic episode, and they never wake up. That’s the worst result, but there are a lot of other really bad things that can happen too.”

After winning the Diabetes Innovation Challenge,  Mahdavi talked with a close friend who was at the event, and had had a recent hypoglycemic episode that landed him in the hospital.  “This is a fifty-five-year-old industry veteran biotech guy who knows insulin inside and out. He’s one of the most well educated people you can find in terms of type 1, and he’s still having this issue,” says Mahdavi. The worst thing about it, the friend told Mahdavi, is that he had absolutely no idea why it happened; he’d gone to bed with an even blood sugar of 110, according to his CGM, and everything seemed fine. It was just one of those strange, unpredictable things that happens now and then with T1D. “He told me if this glucagon is actually developed, it could have a huge effect on the quality of life of type 1s, because everyone is living in fear of hypos. That shows up in so many different ways, including how aggressively people use their insulin.”

But any excitement about the idea has to be balanced by the fact that the concept is at a very early stage, with much to be figured out before it could even be tested at the pre-clinical level. Challenges include preclinical development of the molecule that both senses low blood glucose and switches on at the right moment; and playing with the molecule so it lasts for seven days with adequate strength throughout (their plan is to develop a version that would be injected once a week). Mahdavi points out other challenges too, including that glucagon is unstable and doesn’t dissolve easily. All in all, he says, “Glucagon is a really difficult molecule to work with.” Yet this is exactly the sort of early-stage work that the Diabetes Innovation Challenge was set up to foster, Mahdavi says. “I think the award is really meant to target concepts that are very promising, have high impact, and are in early stages of development. This fits within that category.”

Right now, Mahdavi thinks there may be two other groups in the country working on the concept of smart glucagon. But he wouldn’t be surprised—and wouldn’t mind—if more groups join the hunt. “Every time we talk about what we’re doing, a year or two later there are ten other groups working on it. But my view is, it just doesn’t make sense to hide away what you’re working on and not show it to people.  It doesn’t mean we won’t patent it—we’ll patent the hell out of it—but sometimes competition is beneficial too. At the end of the day, we are trying to solve a problem that many people are faced with and that is the most important goal.”

 

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Ivan

Let me guess, 5 more years.

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