Zealand Pharma updates U.S. on dasiglucagon for congenital hyperinsulinism

Zealand Pharma has announced a key update regarding the regulatory status of its drug dasiglucagon for congenital hyperinsulinism (CHI) in the United States. The U.S. Food and Drug Administration (FDA) has issued a Complete Response Letter (CRL) concerning the New Drug Application (NDA) for dasiglucagon, specifically for its use in preventing and treating hypoglycemia in pediatric patients aged seven days and older for up to three weeks. The CRL was issued due to timing issues related to a reinspection of a third-party manufacturing facility.

The reinspection of this facility took place in August and September 2024, but the facility has not yet received a new inspection classification. Earlier inspections had identified certain deficiencies unrelated to dasiglucagon, which were resolved by the time of the recent reinspection. The FDA's CRL did not raise any concerns regarding the clinical data or the safety of dasiglucagon itself.

David Kendall, Chief Medical Officer of Zealand Pharma, emphasized the company's dedication to addressing the significant unmet medical needs of children with congenital hyperinsulinism, who currently face very limited treatment options. He reaffirmed Zealand Pharma's commitment to collaborating with the FDA and their third-party manufacturing partner to make dasiglucagon available to affected patients as soon as possible.

The regulatory review of dasiglucagon by the FDA is structured into two parts under the same NDA. Part 1, which the CRL addresses, pertains to the drug's use for up to three weeks. Part 2 concerns the administration of dasiglucagon beyond this period. For Part 2, the FDA has requested additional analyses from existing continuous glucose monitoring (CGM) datasets from the Phase 3 clinical trials. Zealand Pharma aims to submit these data by the end of 2024.

Congenital hyperinsulinism is a severe and ultra-rare genetic condition that mainly affects infants and children. It is characterized by the excessive secretion of insulin by dysfunctional pancreatic beta cells, leading to repeated and severe episodes of hypoglycemia. Persistent hypoglycemia can cause serious complications such as seizures, brain damage, and even death. The condition is estimated to affect one in 50,000 or more children, resulting in approximately 180 to 300 new cases annually in the United States and Europe.

Patients with CHI face significant challenges due to the disease, including complex care requirements that often necessitate continuous intravenous glucose infusions and frequent hospitalizations. Diazoxide is the only currently approved medication for hyperinsulinism, but it carries risks such as fluid retention, pulmonary hypertension, and heart failure. Other treatments like glucagon and octreotide may be used but are not officially approved for CHI. More than half of CHI patients do not respond adequately to existing treatments, highlighting the urgent need for new and better therapeutic options.

Dasiglucagon functions as a glucagon receptor agonist, prompting the liver to release stored sugar into the bloodstream. It is designed for continuous subcutaneous infusion using a wearable pump system, developed in collaboration with DEKA Research & Development Corporation. Zealand Pharma continues to advance its product pipeline, with multiple drug candidates in clinical development, two of which are already on the market. The company, founded in 1998 and headquartered in Copenhagen, Denmark, also operates in the U.S. and maintains numerous development and commercial partnerships.