RARE Daily

FDA Issues Complete Response Letter for Zealand’s Dasiglucagon in Congenital Hyperinsulinism

December 29, 2023

Rare Daily Staff

The U.S. Food and Drug Administration issued a Complete Response Letter for Part 1 of the New Drug Application 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 three weeks of dosing.

The CRL addresses deficiencies identified following an inspection at a third-party contract manufacturing facility. These deficiencies are not specific to dasiglucagon. The CRL did not state any concerns about the clinical data package or safety of dasiglucagon.

“We are committed to working closely with the FDA and the third-party manufacturer to resolve these issues so that we can bring dasiglucagon to patients living with this devastating disease who are in need of new treatment options,” said David Kendall, chief medical officer of Zealand Pharma. “Based on our understanding of the FDA’s position, we remain confident in the potential for dasiglucagon to help children and their families affected by congenital hyperinsulinism.”

Congenital hyperinsulinism (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 United States and Europe every year.

CHI has a significant impact on patients’ 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. 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 a glucagon receptor agonist that works by causing the liver to release stored sugar to the blood and is being evaluated for the prevention and treatment of hypoglycemia in infants and children with congenital hyperinsulinism. Dasiglucagon is designed to be administered by continuous subcutaneous infusion using a wearable pump system. Zealand Pharma has a collaborative development and supply agreement with DEKA Research & Development Corporation and affiliates for the wearable subcutaneous infusion pump system.

Zealand expects to resubmit the NDA for dasiglucagon for CHI for up to three weeks of dosing in the first half of 2024 contingent on successful reinspection of the third-party manufacturing facility.

The FDA granted dasiglucagon Priority Review on August 30, 2023, for up to three weeks of dosing. The regulatory review of dasiglucagon is planned to be conducted in two parts under the same NDA. Part 1 relates to dosing of up to 3 weeks and Part 2 relates to the use beyond 3 weeks. Supporting the use of dasiglucagon in CHI beyond 3 weeks, the FDA requested additional analyses from existing continuous glucose monitoring (CGM) datasets, which Zealand still expects to submit in the first half of 2024. CGM was included as a secondary outcome measure in the phase 3 clinical program.

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