Zealand Pharma receives second CRL for glucagon receptor agonist

The FDA has issued a second complete response letter (CRL) to Zealand Pharma concerning their glucagon receptor agonist, dasiglucagon, aimed at treating congenital hyperinsulinism in pediatric patients. This ultra-rare genetic condition leads to an overproduction of insulin, causing dangerously low blood sugar levels. Zealand Pharma reported that the CRL is related to a reinspection of a third-party manufacturing facility. While the reinspection was completed in August or September, the facility's inspection classification is still pending. Importantly, Zealand stated that the FDA's decision is not connected to the safety or clinical data of dasiglucagon.

David Kendall, Zealand's Chief Medical Officer, emphasized the company's dedication to collaborating with the FDA and their manufacturing partner to ensure that dasiglucagon reaches patients struggling with this severe condition in the near future. This is the second time the FDA has rejected the drug, with the first rejection occurring last December. That decision was based on issues identified during an inspection of the same third-party contract manufacturing facility.

Dasiglucagon's regulatory submission is divided into two parts. The first part covers dosing for up to three weeks, while the second part extends beyond three weeks. The recent CRL affects only the first part of the application. The second part is progressing, with Zealand working to provide additional analyses requested by the FDA from existing continuous glucose monitoring data from the Phase 3 trial. The company plans to submit this data by the end of the year.

In 2021, the FDA approved dasiglucagon under the brand name Zegalogue for treating severe hypoglycemia in both adults and children with diabetes. Novo Nordisk holds the license for Zegalogue and oversees its global commercialization.

Dasiglucagon’s development has been closely watched due to its potential to address significant unmet medical needs in congenital hyperinsulinism, offering hope to pediatric patients who face the challenges of this rare disorder. Despite the setbacks related to manufacturing inspections, Zealand Pharma remains optimistic about bringing dasiglucagon to market, aiming to improve the quality of life for those affected by congenital hyperinsulinism. The company continues to work diligently on resolving the manufacturing issues and meeting the regulatory requirements set forth by the FDA.