Zealand Pharma announces designation of priority review by the US FDA for dasiglucagon in congenital hyperinsulinism

Zealand Pharma A/S, a biotechnology company focused on the discovery and development of innovative peptide-based medicines, announced that the US FDA has granted priority review designation for dasiglucagon for the prevention and treatment of hypoglycemia in pediatric patients 7 days of age and older with CHI for up to 3 weeks of dosing.

The regulatory review will be conducted in two parts under the same NDA. Part 1 relates to dosing of up to 3 weeks, whereas Part 2 relates to the use beyond 3 weeks. Supporting the use of dasiglucagon in CHI beyond 3 weeks, the US FDA has requested additional analyses from existing continuous glucose monitoring (CGM) datasets, which are expected to be submitted before the end of the year. CGM was included as a secondary outcome measure in one of the two pivotal Phase 3 clinical trials.

“We are very pleased with the decision of the US FDA to grant priority review for dasiglucagon for the prevention and treatment of hypoglycemia in infants and children with CHI, recognizing the significant and urgent unmet medical need in this patient population”, said David Kendall, MD, Chief Medical Officer of Zealand Pharma.

“We believe that the decision of the FDA to provide such a fast review cycle for the first part of the NDA is a strong testament to the potential value of this product to patients. We remain in close dialogue with the FDA and appreciate the collaborative nature of our work with the agency, recommending a review of the NDA in two parts under the same application to ensure patient access as fast as possible. This approach, and the priority review, underscores the importance of bringing new and better treatment options to the healthcare professionals treating infants and children with CHI. We look forward to continued dialogue with the FDA in generating additional analyses from existing datasets around the use of CGM to be submitted before the end of the year for Part 2 of the NDA review”.

Three Phase 3 clinical trials

The submission of the NDA was based on the results from two pivotal Phase 3 trials and interim results from an ongoing long-term extension trial.

One trial (NCT04172441) evaluated the efficacy and safety of dasiglucagon for subcutaneous infusion in a hospital setting in 12 neonates and infants with CHI aged 7 days to 12 months. In part 1 of this trial, a double-blind placebo-controlled 48 hours crossover study, dasiglucagon reduced the need for intravenous infusion of glucose by 55% compared to placebo. In part 2 of the trial, being 21 days open-label treatment, 10 of the 12 neonates and infants weaned off intravenous glucose for at least 12 hours and 7 of the 12 neonates and infants remained weaned off intravenous glucose at the end of the trial without concomitant pancreatic surgery.

A second trial (NCT03777176) evaluated dasiglucagon for subcutaneous infusion in a homecare setting in 32 children with CHI aged 3 months to 12 years. Dasiglucagon treatment did not significantly reduce the number of intermittent self-measured plasma glucose (SPMG)-measured hypoglycemia events per week when compared to standard of care alone. However, when using continuous glucose monitoring (CGM), dasiglucagon treatment, when added to standard of care therapies, reduced the time in hypoglycemia, defined as glucose <70 mg/dL, by approximately 50% and reduced the number of hypoglycemic events by approximately 40% compared to standard of care treatment alone.

In both clinical trials, dasiglucagon for subcutaneous infusion was assessed to be well tolerated. Skin reactions and gastrointestinal disturbances were the most frequently reported adverse events and 42 of the 44 participants in the two trials continued into the long-term trial (NCT03941236), evaluating dasiglucagon for the treatment of infants and children with CHI.

To ensure the most efficient regulatory review process, the US FDA has recommended reviewing the NDA submission in two parts. Part 1 of the review relates to dasiglucagon for the prevention and treatment of hypoglycemia in pediatric patients 7 days of age and older with CHI for up to 3 weeks of dosing, whereas Part 2 of the review relates to the same indication but for use beyond 3 weeks of dosing. The US FDA has requested additional analyses on the use of CGM from existing datasets supporting the use of dasiglucagon in CHI beyond 3 weeks, which Zealand Pharma expects to submit before the end of the year. Part 2 does not represent a supplemental New Drug Application but is under the same NDA.