Lilly submits NDA for nasal glucagon

Eli Lilly announced the submission of a new drug application to the FDA for investigational nasal glucagon for the treatment of severe hypoglycemia in adults and pediatric patients with diabetes, according to a statement from the company.

Lilly has also submitted a European Union marketing authorization application for nasal glucagon to the European Medicines Agency. If approved, nasal glucagon could be the first nasal dry powder spray rescue treatment for low blood glucose emergencies in people with diabetes.

“Lilly is pleased to announce the regulatory submissions of nasal glucagon to the U.S. Food and Drug Administration and European Medicines Agency,” Thomas Hardy, senior medical director, Lilly Diabetes, told Endocrine Today. “The submissions put us one step closer to bringing this innovative rescue medicine to the diabetes community and filling an important need in the treatment of severe hypoglycemia.”

Glucagon, one of the first-line treatments for severe hypoglycemia in a real-world setting, is unstable in an aqueous form. Available kits contain powdered glucagon that must be reconstituted in a multistep process before the drug can be administered to a patient, and a caregiver may also be required to decide on the correct dose to administer to a child based on his or her body weight.

“Many people can’t use the [currently available] glucagon kit,” Larry C. Deeb, MD, a specialist in pediatric endocrinology at Tallahassee Memorial Healthcare, Florida, told Endocrine Today in an April interview. “It sounds good on paper, but it can be confusing for caregivers.”

Nasal glucagon delivers glucagon as a dry powder spray in a compact, portable, single-use, ready-to-use device. To administer, the caregiver inserts the device tip into a nostril and presses a small plunger at the bottom of the device to release the glucagon dry powder spray in the nose, where the glucagon is passively absorbed through the nasal cavity lining. There is no need for the person with diabetes to inhale or breathe deeply, and nasal glucagon can be used in cases of severe hypoglycemia with nasal congestion, Hardy said.

With nasal glucagon, Deeb said, administration and training are simple.

“Training is 5 minutes — this is what it does, and this is how it works,” Deeb said. “And the concept of a nose spray is not foreign to most people.”

As Endocrine Today previously reported, children with type 1 diabetes who experienced a moderate hypoglycemic event returned to euglycemic status within 30 minutes of receiving nasal glucagon from a caregiver in a real-world setting, according to findings from a small phase 3 study by Deeb and colleagues published in Pediatric Diabetes. The analysis population included 14 patients who experienced 33 moderate hypoglycemic events with neuroglycopenic symptoms, with a blood glucose level less than 70 mg/dL (mean age, 10 years; 64.3% boys; 100% white; mean diabetes duration, 6.3 years; 71.4% on pump therapy; mean total daily insulin dose, 42.3 U). Three of the patients reported experiencing severe hypoglycemia in the preceding year.

For all 33 hypoglycemic events, patients returned to normal status within 30 minutes of nasal glucagon administration. Mean blood glucose for the cohort increased from 55.5 mg/dL (range, 42-70 mg/dL) at baseline to 113.7 mg/dL (range, 79-173 mg/dL) within 15 minutes of nasal glucagon administration. No additional emergency health services, oral carbohydrates or injectable glucagon were required for patients, according to the researchers.

“In the lifetime of an endocrinologist or pediatric doctor, you have the opportunity to see several innovations in diabetes: newer insulins, technologies with continuous monitoring,” Deeb said in an interview. “This is important and different. You don’t want people to get low [blood sugar], but they do. It’s not a pretend problem, and the fact that the science is clear that people don’t know how to treat it makes it a real problem. With this nasal glucagon kit, anyone could rescue them.”

Lilly is in the final stages of development for nasal glucagon and is ensuring manufacturing capabilities are in place to distribute nasal glucagon if approved, according to the company.

“Lilly is committed to bringing nasal glucagon to market as soon as possible, as we believe a simple, ready-to-use approach to treating severe hypoglycemia via nasal delivery could be an important advance for people with diabetes and their caregivers. It may also expand the community of people who could quickly render aid in a rescue situation,” Hardy said. – by Regina Schaffer