The US FDA has assigned a priority review status to dasiglucagon in addressing congenital hyperinsulinism (CHI). The aim of dasiglucagon is to prevent and treat hypoglycemia in pediatric patients 7 days and older who suffer from CHI, with the treatment lasting up to three weeks.
Congenital hyperinsulinism, an extremely rare genetic disorder predominantly affecting infants and children, causes dysfunction in the pancreatic beta cells that secrete excessive insulin, contributing to constant, recurrent, and often severe hypoglycemia episodes. Continuous hypoglycemia episodes can trigger seizures, brain damage, or fatality. It is believed that CHI affects one in every 50,000 (or more) children; this equates to around 180-300 newborns diagnosed with the disease annually in the US and Europe.
The NDA submission was founded on findings from two crucial Phase 3 studies and the provisional outcomes of an ongoing long-term extension trial.
One study (NCT04172441) assessed the effectiveness and safety of dasiglucagon when administered through subcutaneous infusion in a hospital environment, involving 12 neonates and infants with CHI aged between 7 days and 12 months. The first part of this trial was a double-blind placebo-controlled crossover study lasting 48 hours; it showed that dasiglucagon reduced the requirement for intravenous glucose infusion by 55% compared to the placebo. The second part involved a 21-day open-label treatment, during which ten out of twelve participants stopped intravenous glucose for at least twelve hours. Moreover, seven participants remained off intravenous glucose by the trial’s conclusion without any accompanying pancreatic surgery.
A subsequent trial (NCT03777176) examined dasiglucagon delivered via subcutaneous infusion in a home care scenario involving thirty-two children with CHI aged between three months and twelve years. In comparison to the standard of care alone, dasiglucagon did not significantly decrease the frequency of intermittent self-measured plasma glucose (SPMG)-tested hypoglycemia occurrences per week. However, when supplemented with continuous glucose monitoring (CGM), dasiglucagon treatment (alongside standard of care therapies) diminished hypoglycemia duration (glucose levels below 70 mg/dL) by about 50% and decreased the amount of hypoglycemic incidents by approximately 40% compared to standard care alone.
In a company statement, Dr. David Kendall, Chief Medical Officer of Zealand Pharma, expressed appreciation for the FDA’s decision to award priority review to dasiglucagon for the prevention and treatment of hypoglycemia in infants and children affected by it. He acknowledged that this move signifies recognition of a severe and urgent unaddressed medical necessity within this patient demographic.
For more information on other rare genetic disorders, visit our Congenital and Genetics page.
- Thornton PS et al. (2015) Recommendations from the Pediatric Endocrine Society for Evaluation and Management of Persistent Hypoglycemia in Neonates, Infants, and Children, J Pediatr. 2015;167(2):238-45.
- Banerjee I et al. (2022) Correction to: Congenital hyperinsulinism in infancy and childhood: challenges, unmet needs and the perspective of patients and families, Orphanet J Rare Dis. 2022;17:61.
- Arnoux JB et al. (2011) Congenital hyperinsulinism: current trends in diagnosis and therapy, Orphanet J Rare Dis. 2011; 6:63.