Zealand Pharma announces positive results from the Phase 2 trial of glepaglutide in adult patients with short bowel syndrome (SBS).
Glepaglutide is a novel longacting GLP-2 analogue invented and fully owned by Zealand. The trial was initiated in 2016 at Rigshospitalet, University of Copenhagen, Denmark, and the aim was to assess the efficacy, safety and tolerability of different doses of glepaglutide in SBS patients. The primary trial objective was the effect of glepaglutide on patients’ intestinal absorptive capacity, measured as reduction in wet weight fecal output. In addition, a number of relevant secondary endpoints were evaluated, including increase in energy uptake, change in urine output and changes in absorption of electrolytes and macronutrients.
The trial was a proof-of-concept, double-blind, cross-over, dose-finding trial investigating the effect of three different once-daily doses of glepaglutide (10 mg, 1 mg and 0.1 mg). A total of 16 SBS patients completed the trial, and each patient was treated with two different doses of glepaglutide. The first dose was administered over a three-week period, followed by a washout period of four weeks and then treatment with the second dose for a further three weeks.
“Short bowel syndrome is a severe chronic condition where patients need better treatments to improve intestinal absorption. The results of this Phase 2 trial suggest the potential of glepaglutide to provide increases in both energy, fluid and electrolyte absorption. I look forward to contributing to the next clinical development phase,” said Principal Investigator of the Phase 2 trial, Professor Palle Bekker Jeppesen, MD, PhD,
Department of Gastroenterology, Rigshospitalet, University of Copenhagen.
Glepaglutide met the primary study endpoint of reducing fecal wet weight output (ostomy output or diarrhea), with 833 grams/day (P=0.0002) and 593 grams/day (P=0.0021) in the 10 mg and 1 mg dose groups, corresponding to a relative decrease of 30% and 23%, respectively. In addition, glepaglutide also appeared to increase energy absorption (p<0.05) for the combined 10 mg and 1 mg dose group. Pharmacokinetic data confirmed the long half-life of glepaglutide when dosed daily. Glepaglutide was observed to be safe and well tolerated in the trial. The most frequently reported adverse events were nausea, abdominal pain, abdominal distension, vomiting, stoma complications, dizziness, polyuria, decreased appetite, peripheral edema, cough and injection site reactions. Most of these were mild to moderate.
“We now look forward to continuing our dialogue with U.S. and EU regulatory authorities with the aim of taking glepaglutide into Phase 3 clinical development in 2018,” said Adam Steensberg, Executive Vice President, Chief Development and Medical Officer of Zealand.