With Supportive Data, Zealand Looks to NDA for Rare Pediatric Hypoglycemia

Zealand Pharma, a biotech company that creates peptide-based medicines, shared positive top-line results for the second Phase III clinical trial of its congenital hyperinsulinism (CHI) drug, dasiglucagon, in pediatric patients.

The positive data is consistent with Zealand’s first Phase III trial. Though that study ultimately failed to meet the main endpoint, there were optimistic signs under certain conditions. If approved, it would become the first new treatment developed specifically for CHI in over thirty years.

CHI is a rare genetic disease that affects infants and toddlers. Those with CHI have a defect in the gene that produces insulin cells, causing the cells to produce too much insulin and putting the child into a state of hypoglycemia.

Dasiglucagon, a glucagon analog, is stable in aqueous substances so it can be delivered to patients through a continuous infusion pump. It was previously granted orphan drug designation by both the European Commission and the U.S. Food and Drug Administration (FDA).

The second Phase III study is a pivotal, double-blind, placebo-controlled, randomized global trial with 12 pediatric patients ranging in age from 7 days to 12 months old. The main goals of the study are to reduce or eliminate the need for intensive hospital treatment, delay or eliminate the need for a pancreatectomy and reduce the frequency of dangerously low blood glucose.

One unique aspect of the study is that it required the dasiglucagon to be administered through a pump. It is the last in a series of trials that make up the largest clinical development program ever conducted for CHI.

The data demonstrated that dasiglucagon produced a statistically significant difference in helping manage blood glucose levels compared to placebo, meeting the study’s primary endpoint. Dasiglucagon helped reduce the rate of intravenous glucose by 55%. The drug was well-tolerated, and 42 of 44 patients enrolled across the dasiglucagon Phase III programs continued into an ongoing trial focused on safety.

“We are extremely pleased with the top-line results from our second Phase III study of dasiglucagon for the treatment of infants with CHI. CHI is a serious ultra-rare condition with a significant unmet medical need which places a tremendous burden on both patients and families,” said Adam Steensberg, Zealand’s president and CEO.

These results were similar to the data of the first Phase III trial, which was reported in December 2020. In the first Phase III, Zealand tested the drug on 32 children ranging in age from 3 three months to 12 years old. Each trial participant had already had their pancreas removed and/or received maximum medical therapy for CHI, but was still experiencing more than three hypoglycemic events per week.

The study’s endpoint was intermittent self-measured plasma glucose. The data showed that dasiglucagon in combination with standard of care treatments did not significantly affect the rate of hypoglycemia when compared with standard of care by itself. However, dasiglucaton on its own reduced hypoglycemia by 40-50% compared to standard of care when assessed by blinded, continuous glucose monitoring. Additionally, the drug was well-tolerated, and 31 of 32 participants continued into a long-term extension study.

In November 2021, Zealand and DEKA announced a collaboration to use DEKA’s continuous infusion pump to administer dasiglucagon. The agreement stated that Zealand would distribute and commercialize the drug and the pump together, while DEKA would develop and manufacture the pump.

Now, with positive data from two Phase III trials and a pump collaboration under its belt, Zealand has expressed an ambitious next step: to file a New Drug Application with the FDA by the end of 2022.

“We believe the outcome of this trial supports the potential of dasiglucagon as a novel treatment for those living with CHI. We look forward to engaging with the U.S. FDA and moving forward with our New Drug Application,” Steensberg said.