Glepaglutide

Glepaglutide (ZP1848)* is a long-acting, stable and soluble GLP-2 analogue, developed and wholly owned by Zealand Pharma. Glepaglutide is currently in clinical Phase II development for the treatment of short bowel syndrome (SBS).

GLP-2 (glucagon like peptide 2) is a naturally occurring peptide hormone produced primarily by the small intestine. It is secreted together with GLP-1 in response to food ingestion and acts by binding to the GLP-2 receptor, which is predominantly found in the gastrointestinal tract. GLP-2 plays a key role in intestinal growth and formation by promoting regeneration of the epithelial surface of the gut and thus is an obvious therapeutic target in the field of gastrointestinal diseases.

The molecule has been designed to be stable in liquid formulations for easy and convenient daily dosing in an injection pen.

Results from preclinical studies

In preclinical studies, glepaglutide (ZP1848) demonstrated efficacy on small intestine growth and demonstrated the physico-chemical properties of a long-acting, stable and soluble peptide therapeutic with the potential for convenient administration in liquid formulation. Zealand has also investigated glepaglutide in a combined single (SAD) and multiple (MAD) ascending dose Phase I trial. Results from this trial demonstrated that ZP1848 is safe and well tolerated with a supportive effect on bowel function. The attractive potential identified for glepaglutide in SBS and the opportunity for Zealand to initiate a clinical Phase II development program in this specialist care indication is an important step in line with the company’s strategic focus on increasing the value of its proprietary pipeline.

Phase 2 results expected mid 2017
In 2016, Zealand initiated a Phase 2 clinical trial. The trial is a randomized, double-blind, dose-finding trial with crossover design testing the clinical efficacy and safety of three doses of glepaglutide in 18 patients with SBS. Pending the
outcome of this Phase 2 clinical trial, a dialogue with the FDA and the EMA regarding a Phase 3 trial will be initiated later in 2017.

*Glepaglutide is a proposed International Non-proprietary Name (pINN)

Short bowel syndrome

Short bowel syndrome (SBS) is a complex chronic disease characterized by severe or complete loss of bowel function. SBS can result from either physical removal of portions of the small intestine and colon or from loss of function as a result of bowel damage. The primary underlying causes of SBS are Crohn’s disease, ischemia, radiation and colon cancer.

Patients with SBS have reduced intestinal absorption and ability to maintain protein-energy, fluid, electrolyte, or micronutrient balances when on a conventionally accepted, normal diet. Many are therefore dependent on constant parenteral (intravenous) supplements in the form of fluids, salts and nutrition to maintain body homeostasis. Before the 1970s, this group of patients often died because of dehydration and malnutrition. Today, the implementation of parenteral support, including the possibility of home administration, via a catheter placed in a central vein close to the heart, has increased survival and life expectancy for patients with SBS, resulting in high prevalence growth. There are estimated 10-20,000 SBS patients in the US and a similar number in the EU
Patients dependent on regular parenteral support experience a number of serious and life-threatening complications associated with their disease and treatment including shortened life span, high risk of sepsis, blood clots or liver damage, and reduced quality-of-life due to the time required for and consequences of frequent access to an intravenous pump.

Teduglutide (Gattex®/ Revestive®), a GLP-2 receptor agonist, was approved in 2012 and launched in 2014 in both the US and Europe as the first medicine indicated for the treatment of SBS.


About glp-2 agonists

GLP-2 (glucagon like peptide 2) is a naturally occurring peptide hormone produced primarily by the small intestine. It is secreted together with GLP-1 in response to food ingestion and acts by binding to the GLP-2 receptor, which is predominantly found in the gastrointestinal tract. GLP-2 plays a key role in intestinal growth and formation by promoting regeneration of the epithelial surface of the gut and thus is an obvious therapeutic target in the field of gastrointestinal diseases.

GLP-2 peptide drugs have gained increased interest over recent years building partly on the clinical advance of the degradation-resistant GLP-2 analogue, teduglutide (trade name Gattex /Revestive® ex. North America), developed by NPS Pharmaceuticals and Nycomed (now Takeda). The European Medicines Authority (EMA) recommended approval of teduglutide for the treatment of Short Bowel Syndrome in June 2012 and it was then approved by the FDA in December 2012, making this the first GLP-2 based peptide drug to be commercialized.