September 15, 2015

STOCKHOLM — New data on a needle-free nasal delivery system for glucagon for use in severe hypoglycemia presented at the European Association for the Study of Diabetes (EASD) 2015 Meeting here today appear promising, and the Canadian company developing the product say it hopes to file a US new drug application (NDA) next year.

Claude Piché, DVM, MSc, of Locemia Solutions, Montreal, Quebec, reported the findings of a small study showing that needle-free nasal delivery of glucagon was faster and had a much higher success rate with fewer errors than delivery of glucagon via injection when given either by caregivers of diabetes patients or "good Samaritan" bystanders, in a simulation of severe hypoglycemia situation using a manikin.

And Jennifer Sherr, MD, of Yale School of Medicine in New Haven, Connecticut, also reported on use of intranasal glucagon in children with type 1 diabetes, replicating a presentation she made at the American Diabetes Association meeting in Boston in June. She demonstrated that a 3-mg intranasal dose of glucagon was safe and effective across the age range of 4 to 17 years.

She explained that patients do not need to be able to consciously inhale the glucagon powder, as it is absorbed passively, so this is not a limiting factor when dealing with unconscious patients. The powder is also thought to be stable at room temperature and to have a shelf life of about 2 years.

Dr Sherr, who, as well as taking care of children with diabetes, also lives with type 1 herself, told Medscape Medical News: "As a clinician, we frequently get phone calls for severe hypoglycemia, and people haven't treated it because they don't know where the [glucagon] kit is, and so I think this makes the potential treatment much easier for parents, schoolteachers, bus drivers — anybody can do it.

"And as somebody who lives with type 1, it's something I would carry — I'm here in Stockholm with nobody with me," for example, she added.

Following her presentation, one attendee commented, "This is great, as glucagon is so often not given," and another said, "This may be really important" and suggested the product could one day be carried by emergency vehicles.

Asked to comment, Clifford J Bailey, PhD, of Aston University, Birmingham, United Kingdom, who was one of the chairs of the session during which Dr Sherr presented her findings, said: "Intranasal glucagon sounds interesting and is potentially a very attractive option, because it can be very quickly administered. But we have yet to see data that would tell us exactly how it is getting in, because most nasally administered peptides require an absorption enhancer. I don't know whether [this] formulation has one."

And, he added to Medscape Medical News, "We also need some experience of how many shots, how often, you give, depending on how low you go. And…we can estimate that there are differences in the nasal mucosa during development, during periods of infection, and all of those things, which will need to be looked at."

Fear of Hypoglycemia

Dr Sherr explained that the current treatment for severe hypoglycemia, which can cause seizures and loss of consciousness, requires the reconstitution of glucagon prior to intramuscular injection and must be dosed by weight, a process that is prone to error.

Although parents are often confident to use intramuscular glucagon in such situations, children with type 1 diabetes are often in the care of others, including grandparents, babysitters, siblings, school nurses, and teachers, who may feel less able to administer this. As a result, glucagon is often underused in the setting of severe hypoglycemia, she noted.

And as such, fear of hypoglycemia is a major barrier to the attainment of glycemic control targets in patients with type 1 diabetes, which in turn may affect patients' and their parents' quality of life.

She acknowledged, however, that, in her study, the product was administered by trained healthcare professionals, and therefore "this may not reflect the experience of…nonmedical users," she noted.

But the research reported by Dr Piché demonstrated that nonmedical caregivers, as well as untrained acquaintances, could also successfully treat the condition with nasally administered glucagon, she noted.

Fewer Errors With Intranasal Glucagon

In his poster, Dr Piché explained that 16 adult insulin-using patients with diabetes (median age, 57 years) and their caregivers were taught how to use both the nasal glucagon-delivery system and the commercially available injected glucagon, in random order.

One week later, the caregivers were asked to treat a manikin during a simulated episode of severe hypoglycemia — sound effects and distractions were employed to create a sense of urgency, and the caregivers were told they had to administer rescue glucagon as quickly as possible, he explained.

They were instructed to find the rescue glucagon kit being evaluated in the manikin's backpack, which also contained personal effects and a diabetes-supply pouch (containing glucose meter and strips, alcohol swabs, lancing device, insulin vial, and syringe).

Of the 16 caregivers, 15 successfully delivered a full dose of glucagon with the nasal system, with an average time of 16 seconds. One person failed to fully depress the plunger on the nasal system (but this person also failed to inject conventional glucagon).

In contrast, only two of the 16 caregivers delivered a full, conventional intramuscular dose of glucagon, and six gave a partial dose (average time 1 minute 53 seconds). Eight caregivers failed to deliver any glucagon this way. Failures included injection of diluent only and bent needles.

In addition, two caregivers used insulin rather than glucagon.

The investigators then went on to recruit 15 adults, good Samaritans not associated with any person with diabetes, who said they were willing to assist someone in distress. They were not trained on the devices but were simply shown how to use the respective products prior to the simulation. They treated two episodes of severe hypoglycemia in the manikin with either the nasal system or conventional glucagon injection, in random order with a delay of about 10 minutes between each simulation.

Of the 15 good Samaritans, 14 delivered a full dose of glucagon with the nasal system, with an average time of 26 seconds. One who failed to fully depress the plunger on the nasal system also failed to inject the conventional glucagon.

In fact, none of them administered a full dose of intramuscular glucagon; three gave a partial dose (average time of 2 minutes 24 seconds), 12 failed to deliver any, and one used insulin by mistake instead of glucagon.

The needle-free delivery of glucagon is therefore "faster and has a much higher success rate with fewer errors than delivery by injection for nonmedical caregivers of people with diabetes" in a severe hypoglycemia simulation, said Dr Piché.

In addition, untrained acquaintances were also able to deliver nasal glucagon successfully, at a similar rate to trained caregivers, highlighting the simplicity, intuitiveness, and ease of use of the needle-free system, he concluded, adding that the nasal mode of delivery, being different from that of insulin, may also reduce the risk of confusion and accidental delivery of insulin.

Brian Frier, the moderator of the poster session during which Dr Piché presented his findings, observed what a disaster it could be when non–medically trained people were asked to give glucagon, with some administering insulin instead.

He said he was impressed by the "ease" of giving glucagon by the nasal route.

European Association for the Study of Diabetes 2015 Meeting. Stockholm, Sweden. Abstract 42 and Abstract 867, presented September 15, 2015.

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