Rie Schultz Hansen
Vice President, Research, Zealand Pharma
Glepaglutide – a Novel Long-Acting GLP-2 Analog for the Treatment of Short Bowel Syndrome
Glucagon-like peptide (GLP-2) is an intestine-derived peptide that is rapidly deactivated and cleared from the circulation (T½ = ~7 min). GLP-2 positively modulates the morphology and function of the small intestine in both healthy and diseased conditions.
Short bowel syndrome (SBS) is a condition characterized by malassimilation in part due to reduced intestinal surface area following resection of the intestines primarily as a result of cancer, Crohn’s disease or trauma. SBS patients need to supplement their food intake with long periods of time receiving parenteral nutrition. Glucagon-like peptide-2 (GLP-2) exerts mucosal growth-promoting effects mediated via stimulation of crypt cell proliferation and inhibition of villus cell apoptosis. In SBS patients, treatment with GLP-2 has been shown to improve intestinal absorption by increasing intestinal mucosal surface area and possibly by slowing gastrointestinal emptying and reducing gastrointestinal secretions.
Zealand is developing glepaglutide (ZP1848) a novel, potent and biologically stable GLP-2 receptor agonist in a ready-to-use liquid formulation for the treatment of SBS. Glepaglutide has successfully completed Phase II clinical studies using daily administration, demonstrating significant effects on reducing fecal wet weight output, increasing fluid absorption and reducing urine output, a secondary endpoint that guides reduction in parenteral support. In addition glepaglutide has been shown to have a T1/2 of approximately 50 hours indicting the potential for a reduced dosing frequency. The pivotal Phase 3 trial for glepaglutide, EASE SBS 1 (Efficacy And Safety Evaluation of glepaglutide in treatment of SBS), was initiated in 2018 and results are expected in 2020. The 24-week trial will enroll 129 patients with short bowel syndrome to test efficacy and safety of once- and twice weekly dosing with glepaglutide.
Rie Schultz Hansen holds a PhD in medicinal research and is Vice President, Research at Zealand Pharma, Denmark, with 18 years of work experience from smaller biotech companies. Working for Zealand Pharma for the last 8 years, the focus of Rie Schultz Hansen’s research and industrial work has been to discover and develop innovative new peptide medicines for the treatment of metabolic, inflammatory and gastrointestinal diseases and she is the author of more than 50 publications, published conference reports and patent applications.