Glucagon

SAN ANTONIO — Zealand Pharma, hoping to create the next “foundational” therapy for obesity, detailed more Phase 1 data on its amylin analog that was the backbone of a $1 billion raise this summer. Researchers said Zealand’s drug, dubbed petrelintide, led to up to 8.6% mean weight loss in an early-phase trial. Also, all gastrointestinal disorders observed in the study were mild, save for a moderate case of nausea and a moderate incidence of vomiting. The data were presented Tuesday at the annual ObesityWeek conference in Texas. Zealand initially toplined the data in June and quickly raised $1 billion for the “ crown jewel .” Analysts have predicted petrelintide could reach peak sales of $10 billion. At week 16 in the Phase 1, patients on 2.4 mg petrelintide lost a mean 4.8% body weight. The middle-dose group, 4.8 mg, lost the most at 8.6%, and the 9 mg group saw 8.3% reductions, the researchers said. The drop was 1.7% for the placebo cohort. Petrelintide could potentially have GLP-1-like weight loss of 15% to 20% in larger studies, Zealand chief medical officer David Kendall told Endpoints News on the sidelines of the conference. It also believes amylin agonists could help preserve lean muscle mass, an issue that has come up with the GLP-1 class. The company will dose the first patient in a Phase 2 trial in the coming days or weeks, Kendall said. The study will “elucidate” the differences between the 4.8 mg and 9 mg doses, he said. Zealand is positioning the drug as a potential standalone replacement for GLP-1s or as the first medicine that patients go to for obesity, but the company isn’t excluding the opportunity to combine with GLP-1s or other mechanisms, Kendall said. Novo Nordisk and Eli Lilly have dominated the field so far, but their GLP-1-based medicines carry GI tolerability baggage, among other challenges. Rather than suppress appetite and give patients a “food aversion” signal like the GLP-1s, amylin emphasizes the satiety signal, Kendall said. In his career, he’s worked in both the amylin field at Amylin Pharmaceuticals and on GLP-1s and other mechanisms at Lilly. “If you’ve had a meal here in Texas, you know what satiety feels like. That sense of, I’ve had enough, maybe a little bit too much,” Kendall said. “It actually enhances that signal so you don’t have that same food aversion, the lack of interest. So people tend to eat.” Petrelintide has a 240-hour half-life, or about 10 days, Kendall said. Novo, Lilly, AstraZeneca and multiple other drugmakers are also working on amylin. The field awaits a key Phase 3 readout this quarter from Novo’s CagriSema, a combination of the amylin asset cagrilintide and its blockbuster semaglutide. Novo’s amylin drug “will always be tied to semaglutide,” Kendall said. “We see petrelintide as the next potentially foundational class of therapies going forward. I know it seems maybe aspirational to say over and above what is a pretty successful GLP-1-based therapeutic class.” Structure Therapeutics, which plans to start testing its amylin candidate in humans next year, is looking up to Zealand’s progress. “Zealand is probably the pioneer in terms of pushing the monotherapy as part of their strategy,” Structure CEO Raymond Stevens said in an interview on the sidelines of the conference. “Some of the hypothesis is: amylin has the potential for better tolerability by itself, amylin alone, versus GLP-1.” As Zealand works on the Phase 2, it is looking for a large pharma to help carry petrelintide into Phase 3 and make it a standalone drug. With a fresh $1 billion, though, Zealand is “not backs-against-the-wall,” Kendall said. “The most important thing is not just to find someone with lots of people and deep pockets, but someone who believes in the positioning we’ve talked about.” Zealand already has a partner for its lead obesity drug, the Boehringer Ingelheim-allied survodutide, a glucagon/GLP-1 receptor dual agonist.

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.