Glucagon

Zealand Pharma provides U.S. regulatory update on dasiglucagon in congenital hyperinsulinism U.S. Food and Drug Administration (FDA) issues Complete Response Letter (CRL) for dasiglucagon in CHI for up to three weeks of dosing due to the timing of a third-party manufacturing facility reinspection The reinspection of the facility was completed in August/September 2024 for which a new inspection classification is pending Zealand remains committed to working with the FDA and the third-party manufacturer to bring dasiglucagon to patients in the U.S. as soon as possible October 9, 2024 – Zealand Pharma A/S (Nasdaq: ZEAL) (CVR-no. 20045078), a biotechnology company focused on the discovery and development of innovative peptide-based medicines, today announced that the U.S. Food and Drug Administration (FDA) has issued a Complete Response Letter (CRL) for Part 1 of the New Drug Application (NDA) for dasiglucagon for the prevention and treatment of hypoglycemia in pediatric patients 7 days of age and older with congenital hyperinsulinism (CHI) for up to 3 weeks of dosing. The CRL is related to the timing of a reinspection at a third-party contract manufacturing facility that was completed in August/September 2024. The third-party manufacturer has not yet received its inspection classification following the reinspection. A prior inspection of the facility had identified deficiencies that did not involve dasiglucagon. These prior deficiencies had been resolved as of this reinspection. The CRL did not state any concerns about the clinical data package or safety of dasiglucagon. “We at Zealand Pharma are acutely aware of the significant unmet medical need for newborns and children with congenital hyperinsulinism who have either no or very limited treatment options today,” said David Kendall, M.D., Chief Medical Officer of Zealand Pharma. “We are committed to working with the FDA and our third-party manufacturing partner to bring dasiglucagon to patients living with this devastating disease in the months ahead.” The regulatory review of dasiglucagon is being 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 from the Phase 3 clinical program. Zealand expects to submit these data by the end of 2024. 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.1,2 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 US and Europe every year.3,4 CHI has a significant impact on patient 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, pulmonary hypertension, and congestive heart failure.5 Glucagon and the somatostatin analog octreotide may be used but are not approved therapies. It is estimated that more than 50% 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.6 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 Pharma A/S (Nasdaq: ZEAL) ("Zealand") is a biotechnology company focused on the discovery and development of peptide-based medicines. More than 10 drug candidates invented by Zealand have advanced into clinical development, of which two have reached the market and three candidates are in late-stage development. The company has development partnerships with a number of pharma companies as well as commercial partnerships for its marketed products. Zealand was founded in 1998 and is headquartered in Copenhagen, Denmark, with a presence in the U.S. For more information about Zealand’s business and activities, please visit www.zealandpharma.com. References 1) Thornton PS et al. (2015) Recommendations from the Pediatric Endocrine Society for Evaluation and Management of Persistent Hypoglycemia in Neonates, Infants, and Children, J Pediatr. 2015;167(2):238-45. 2) Banerjee I et al. (2022) Correction to: Congenital hyperinsulinism in infancy and childhood: challenges, unmet needs and the perspective of patients and families, Orphanet J Rare Dis. 2022;17:61. 3) Arnoux JB et al. (2011) Congenital hyperinsulinism: current trends in diagnosis and therapy, Orphanet J Rare Dis. 2011; 6:63. 4) Yau et al. (2020) Using referral rates for genetic testing to determine the incidence of a rare disease: The minimal incidence of congenital hyperinsulinism in the UK is 1 in 28,389, Plos One. 2020;15(2). 5) PROGLYCEM® (diazoxide) oral suspension package insert (07/18/2024) https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/017453s024lbl.pdf (accessed October 7, 2024) 6) Yorifuji et al. (2017) Clinical practice guidelines for congenital hyperinsulinism, Clin Pediatr Endocrinol. 2017;26(3):127-152. The content above comes from the network. if any infringement, please contact us to modify.

iStock, Odairson Antonello The rejection is related to the timing of the FDA’s reinspection of Zealand’s third-party manufacturer, which previously had deficiencies. The FDA on Tuesday denied approval for Zealand Pharma’s dasiglucagon, which the Danish biotech was proposing for the treatment of congenital hyperinsulinism. According to the company’s announcement, the rejection is due to the timing of the FDA’s reinspection of a third-party contract manufacturer. In an initial visit, the FDA flagged “deficiencies” in the outside manufacturer that had been resolved by the time of its second inspection. However, Zealand’s service provider has yet to receive its inspection classification after the regulator’s second visit in August/September 2024. The FDA did not identify concerns regarding dasiglucagon’s clinical data package, nor did it find safety issues with the drug candidate. CMO David Kendall said in a statement that Zealand will continue working with its contract manufacturer and the FDA to “bring dasiglucagon to patients living with this devastating disease in the months ahead.” Congenital hyperinsulinism (CHI) is an ultrarare genetic disease that affects one out of 50,000 children. In the U.S. and Europe, around 180 to 300 newborns are diagnosed with CHI every year. CHI develops when beta cells in the pancreas are dysfunctional and secrete too much insulin. Patients suffer from frequent and severe hypoglycemic episodes, which in turn can lead to seizures, brain damage and even death. Currently, the only FDA-approved therapy for hyperinsulinism is the potassium channel activator diazoxide, which carries risks of fluid retention, congestive heart failure and pulmonary hypertension. Other patients are given glucagon or ocreotide, but these are not approved for CHI. Patients with CHI “have either no or very limited treatment options today,” Kendall said. Zealand’s answer to CHI is dasiglucagon, a glucagon receptor agonist that works by triggering the secretion of stored sugars from the liver. This mechanism of action allows dasiglucagon to counteract the excess insulin typical in CHI patients. In May 2022, Zealand posted Phase III CHI data for dasiglucagon, touting a 55% reduction in the need for intravenous glucose versus placebo. Dasiglucagon is approved for the treatment of severe hypoglycemia in diabetes patients, for which it is marketed under the brand name Zegalogue. The FDA is reviewing Zealand’s CHI application for dasiglucagon in two parts . The first, which was handed the rejection on Tuesday, covers dosing for up to three weeks. The second part is for dasiglucagon dosing beyond three weeks, for which Zealand expects to analyses by the end of 2024.