The U.S. Food and Drug Administration (FDA) has issued a Complete Response Letter (CRL) regarding Zealand Pharma A/S's New Drug Application (NDA) for dasiglucagon, intended for the prevention and treatment of hypoglycemia in pediatric patients aged 7 days and older with congenital hyperinsulinism (CHI). The CRL applies specifically to the use of dasiglucagon for up to three weeks of dosing.
The FDA's decision is attributed to findings from an inspection at a third-party contract manufacturing facility. According to Zealand Pharma, the deficiencies noted during the inspection are not specific to dasiglucagon itself. Importantly, the CRL did not raise any concerns regarding the clinical data package or the safety profile of dasiglucagon.
David Kendall, M.D., Chief Medical Officer of Zealand Pharma, stated the company's commitment to working with the FDA and the third-party manufacturer to resolve the identified issues. He expressed confidence in dasiglucagon's potential to address the needs of children and families affected by CHI.
Regulatory Pathway and Next Steps
Zealand Pharma anticipates resubmitting the NDA for dasiglucagon for CHI (up to three weeks of dosing) in the first half of 2024, contingent on a successful reinspection of the third-party manufacturing facility. The FDA had previously granted Priority Review for dasiglucagon on August 30, 2023, for the specified dosing duration.
The regulatory review process for dasiglucagon is structured in two parts under the same NDA. Part 1 focuses on dosing up to 3 weeks, while Part 2 addresses usage beyond 3 weeks. To support the latter, the FDA has requested additional analyses from existing continuous glucose monitoring (CGM) datasets, which Zealand Pharma expects to submit in the first half of 2024. CGM was included as a secondary outcome measure in the Phase 3 clinical program.
About Congenital Hyperinsulinism
Congenital hyperinsulinism (CHI) is a rare genetic disorder characterized by the excessive secretion of insulin from pancreatic beta cells, leading to frequent and severe hypoglycemic episodes. It is estimated to affect approximately 1 in 50,000 children, resulting in 180-300 new cases annually in the US and Europe. Persistent hypoglycemia in CHI patients can result in seizures, brain damage, and even death.
The current standard of care includes diazoxide, but its use can be limited by side effects such as fluid retention, hypertension, and acute heart failure. While glucagon and octreotide are sometimes used off-label, a significant portion (over 50%) of CHI patients do not respond adequately to available medical treatments, highlighting the need for improved therapeutic options.
Dasiglucagon: A Potential New Treatment Option
Dasiglucagon is a glucagon receptor agonist designed to stimulate the liver to release stored glucose into the bloodstream. It is being developed for continuous subcutaneous infusion via a wearable pump system for the prevention and treatment of hypoglycemia in infants and children with CHI. Zealand Pharma has a collaborative agreement with DEKA Research & Development Corporation for the development and supply of the wearable infusion pump.
