Zealand Pharma submits NDA to the FDA for glepaglutide, a long-acting GLP-2 analog, in short bowel syndrome.

“Short bowel syndrome with intestinal failure is a complex, chronic and severe condition in which individuals are dependent on receiving fluids and nutrition parenterally. While life-sustaining, parenteral support poses significant restrictions on daily life and carries a risk of serious and life-threatening complications. More effective and convenient treatments to further reduce parenteral support are needed, with the ultimate goal of discontinuing parenteral support and achieving enteral autonomy,” said David Kendall, MD, Chief Medical Officer of Zealand Pharma. “We believe glepaglutide, once approved, can reduce both the burden of parenteral support and of daily dosing of existing GLP-2 treatment for people living with SBS and intestinal failure, and we are pleased to submit this treatment for regulatory review and potential approval in the US.”

About EASE Clinical Trial Program : The submission is based on the results from a pivotal Phase III trial (EASE-1), supported by interim results from two ongoing long-term extension trials (EASE-2 and EASE-3), and a mechanistic trial (EASE-4). EASE-1 (NCT03690206) was a randomized, double-blind Phase III trial that evaluated the safety and efficacy of once- and twice-weekly subcutaneous administration of glepaglutide 10 mg compared to placebo in 106 SBS patients with intestinal failure who were dependent on parenteral support (PS) at least three days per week.

Glepaglutide given twice weekly significantly reduced the total weekly volume of PS at 24 weeks as compared to placebo (p=0.0039) in this trial. When administered once weekly, glepaglutide treatment also resulted in a numeric reduction in weekly PS, however this did not achieve statistical significance. At 24 weeks, the average reduction in PS from baseline was 5.13 liters/week for patients treated with glepaglutide twice weekly and was 3.13 liters/week for patients treated with glepaglutide once weekly. Placebo treatment resulted in a reduction in PS of 2.85 liters/week. A total of 9 patients treated with glepaglutide were completely weaned off PS (enteral autonomy), while no placebo-treated patients were able to discontinue PS. For patients treated with glepaglutide twice-weekly, 14% of patients (n=5) achieved enteral autonomy.

Patients who completed EASE-1 could enroll in the extension trials, EASE-2 and subsequently EASE-3, designed to assess long-term safety and efficacy of glepaglutide. EASE-2 (NCT03905707) is a randomized, double-blind trial in which SBS patients continued their randomly assigned treatment from EASE-1 with glepaglutide 10 mg once or twice weekly. Patients who received placebo in EASE-1 were re-randomized to treatment with either glepaglutide 10 mg once or twice weekly. In an interim analysis conducted when all patients had completed at least six months of treatment, clinical response to glepaglutide across the key efficacy endpoints was generally maintained or showed continued improvement, including additional patients on both doses weaning off PS. EASE-3 (NCT04881825) is evaluating glepaglutide administered once weekly using an auto-injector. An interim analysis of EASE-3, conducted with the first 43 patients rolled over from EASE 2, showed that the reduction in prescribed PS was generally maintained. EASE-4 (NCT04991311) is a Phase IIIb trial to assess mechanistic effects of glepaglutide on intestinal fluid and energy uptake. Glepaglutide appeared to be safe and was well-tolerated in all trials. The most frequently reported adverse events were injection site reactions and gastrointestinal events.