FDA Grants Priority Review for Zealand’s Dasiglucagon in Congenital Hyperinsulinism

Rare Daily Staff

The U.S. Food and Drug Administration has granted priority review designation for Zealand Pharma’s dasiglucagon for the prevention and treatment of hypoglycemia in pediatric patients 7 days of age and older with congenital hyperinsulinism for up to 3 weeks of dosing.

The regulatory review will be conducted in two parts under the same New Drug Application. Part 1 relates to dosing of up to three weeks, whereas part 2 relates to the use beyond three weeks. The FDA has requested additional analyses from existing continuous glucose monitoring (CGM) datasets that support the use of dasiglucagon in congenital hyperinsulinism (CHI) beyond three weeks, which are expected to be submitted before the end of the year. CGM was included as a secondary outcome measure in one of the two pivotal phase 3 clinical trials.

“We believe that the decision of the FDA to provide such a fast review cycle for the first part of the NDA is a strong testament to the potential value of this product to patients,” said David Kendall, chief medical officer of Zealand Pharma. “We remain in close dialogue with the FDA and appreciate the collaborative nature of our work with the agency, recommending a review of the NDA in two parts under the same application to ensure patient access as fast as possible. This approach, and the priority review, underscores the importance of bringing new and better treatment options to the healthcare professionals treating infants and children with CHI.”

CHI is a severe, ultra-rare genetic disease, primarily affecting infants and children, in which the pancreatic beta cells dysfunction and secrete too much insulin, leading to frequent, recurrent, and often severe episodes of hypoglycemia. Persistent episodes of hypoglycemia can result in seizure, brain damage and death. It is estimated that CHI develops in one out of 50,000 (or more) children, corresponding to 180-300 newborns being diagnosed with the disease in the U.S. and Europe every year.

CHI has a significant impact on patient quality of life. Complex care requirements, including continuous intravenous infusion of glucose, can result in lengthy and frequent hospitalizations and make daily social activities difficult for both patients and their families. The only currently approved medical treatment for hyperinsulinism is diazoxide, which can be associated with increased risk of fluid retention, hypertension, and acute heart failure. Glucagon and the somatostatin analog octreotide may be used but are not approved therapies. It is estimated that more than 50 percent of CHI patients do not respond adequately to the medical treatment options currently available, so there remains a significant unmet medical need for more and better treatment options.

Dasiglucagon is being investigated by Zealand Pharma for subcutaneous continuous infusion using a wearable pump system as a potential treatment of CHI. Dasiglucagon is a glucagon receptor agonist that works by causing the liver to release stored sugar to the blood. Zealand Pharma has a collaborative development and supply agreement with DEKA Research & Development and affiliates for the wearable subcutaneous infusion pump system.

The submission of the NDA was based on the results from two pivotal phase 3 trials and interim results from an ongoing long-term extension trial. One trial evaluated the efficacy and safety of dasiglucagon for subcutaneous infusion in a hospital setting in 12 neonates and infants with CHI aged 7 days to 12 months. In part 1 of this trial, a double-blind placebo-controlled 48 hours crossover study, dasiglucagon reduced the need for intravenous infusion of glucose by 55 percent compared to placebo. In part 2 of the trial, being 21 days open-label treatment, 10 of the 12 neonates and infants weaned off intravenous glucose for at least 12 hours and 7 of the 12 neonates and infants remained weaned off intravenous glucose at the end of the trial without concomitant pancreatic surgery.

A second trial evaluated dasiglucagon for subcutaneous infusion in a homecare setting in 32 children with CHI aged 3 months to 12 years. Dasiglucagon treatment did not significantly reduce the number of intermittent self-measured plasma glucose (SPMG)-measured hypoglycemia events per week when compared to standard of care alone. However, when using continuous glucose monitoring (CGM), dasiglucagon treatment, when added to standard of care therapies, reduced the time in hypoglycemia, defined as glucose <70 mg/dL, by approximately 50 percent and reduced the number of hypoglycemic events by approximately 40% compared to standard of care treatment alone.

In both clinical trials, dasiglucagon for subcutaneous infusion was assessed to be well tolerated. Skin reactions and gastrointestinal disturbances were the most frequently reported adverse events and 42 of the 44 participants in the two trials continued into the long-term trial, evaluating dasiglucagon for the treatment of infants and children with CHI.

Dasiglucagon injection was approved as Zegalogue by the FDA in 2021 for the treatment of severe hypoglycemia in adults and children with diabetes aged 6 years and older. In June 2023, Zealand submitted a Marketing Authorization Application (MAA) to the European Medicines Agency (EMA) for dasiglucagon injection for the treatment of severe hypoglycemia in adults, adolescents and children aged 6 years and over with diabetes. Zealand Pharma entered a global license and development agreement with Novo Nordisk in September 2022 for the commercialization of dasiglucagon injection for treatment of severe hypoglycemia in people with diabetes. Zegalogue is a registered trademark of Novo Nordisk.

Photo: David Kendall, chief medical officer of Zealand Pharma