While insulin and insulin pumps have evolved into highly technical and effective tools for treating diabetes, the method for delivering emergency glucagon to save the lives of people with diabetes in the throes of hypoglycemia has remained in the relative Stone Age. Until now.
A new system from pharmaceutical firm Eli Lilly and Company for delivering glucagon in a simple, one-use nasal powder rather than in the existing clunky and complicated system that involves mixing liquid and powder together then injecting the solution is now in the final stages of clinical testing.
“Asking anyone to mix and inject emergency glucagon the way it’s always been configured is really scary,” says Robert Oringer, who as part of the pharmaceutical company Locemia was instrumental in developing a new and easier way for family, friends, or any willing person to deliver glucagon rescue to insulin users requiring low blood sugar assistance. “And that’s not right because anyone who uses insulin faces the possibility of low blood sugar. They shouldn’t have to worry about being able to get glucagon when they need it. So, we came up with a better way for them to get it.”
The need to come up with a better system has been apparent for years, even to Lilly, the company that is developing what is called “nasal glucagon” while also owning rights to an existing configuration for delivering glucagon.
In October 2015, Lilly and Locemia announced that Lilly acquired worldwide rights to Locemia’s nasal glucagon. Lilly then set out to commercialize Locemia’s drug and device, according to a spokesperson for Lilly. Since October 2015, the Lilly team has made progress toward ensuring manufacturing capabilities are in place to distribute nasal glucagon worldwide while also preparing for global regulatory submissions. The company expects U.S. regulatory submission to occur in the first half of 2018 and the European Union and Canada submission following. These efforts, if successful, will replace a method of glucagon that is badly in need of improvement.
“The system as it exists now is very complicated,” says Cristina Guzman, MD, Senior Medical Advisor at Lilly “It takes eight or nine steps just to administer. Because of that, it’s not as effective as it might otherwise be.”
Guzman should know how difficult it is work with the existing formulation of glucagon because Lilly is the leading global seller of emergency glucagon kits. The kit comes in a red case with a syringe pre-filled with liquid and a vial of powdered glucagon. On its own website Lilly lays out the following steps on how to use this kit to deliver glucagon to someone who is in hypoglycemic distress and cannot deliver it themselves:
“1. Flip the seal from the vial of Glucagon powder.
- Remove the needle cover from the syringe. DO NOT REMOVE THE PLASTIC CLIP FROM THE SYRINGE, as this may allow the push rod to come out of the syringe.
- Insert the needle into the rubber stopper on the vial, then inject the entire contents of the syringe into the vial of glucagon powder.”
There then follows six more steps that include mixing the glucagon, injecting the glucagon, and then disposing of the one-use set up. All this, keep in mind, is being done while a person with diabetes may be suffering a severe hypoglycemic episode that could include seizures and/or loss of consciousness.
It was this complexity, and a desire to protect his two sons who have diabetes, that prompted Oringer to work on developing a system—any system—better than the one that existed.
Before his two sons were born Oringer had made a living developing and selling products for people living with diabetes in the U.S. “I was one of the first people to do private label lancets, syringes, glucose test strips, and other products initially for independent pharmacies, then regional and small pharmacy chains, and eventually large chains like Walgreens, CVS, and Walmart,” he says. “People referred to me as ‘the private label diabetes guy’ in the 90s.”
Then, in the late 1990s his first son, aged three, and his second son, aged nine months, were both diagnosed with diabetes.
“It was ironic—sadly ironic—but, more than that, it put me on guard.”
What he guarded against most was the need for reviving either of his sons if they suffered a severe hypoglycemic episode. Then, one day while discussing the problem of glucagon delivery with colleagues and a key advisor, Oringer and his team had what he calls an epiphany.
“Glucagon is in powder form,” he says. “It struck us that maybe it doesn’t have to be mixed. After all, there are other drugs that people take in powder form that hit them directly, yes? And, if it doesn’t have to be mixed, maybe it doesn’t have to be injected.”
In 2015 Lilly acquired the rights to Locemia’s nasal glucagon.
In clinical trials results released in June Lilly said that 95.7% of patients who used the nasal glucagon responded with blood sugar levels close to normal within 30 minutes of taking the powdered glucagon.
The new formulation, which does not yet have a name, also does not require patients to inhale the powder, Guzman says. It’s absorbed into the cells of the nasal mucosa.
“I am really excited to be a part of this effort,” Guzman says. “At Lilly we’ve had a long history with diabetes. We made the first commercially available insulin. And this is just another step in our commitment to helping people with diabetes.”
Oringer is likewise pleased that his idea has evolved to become something people can benefit from.
“I hope everyone carries it,” he says, “and that no one ever has to use it.”