New drug application

Citation

(2009), "New drug application", Nutrition & Food Science, Vol. 39 No. 4. https://doi.org/10.1108/nfs.2009.01739dab.011

New drug application

Article Type: Food facts From: Nutrition & Food Science, Volume 39, Issue 4

Zealand Pharma advances ZP1848, a glucagon-like peptide-2 (GLP-2) agonist, into Phase I clinical trials. ZP1848, a peptide, is developed as a therapy for the prevention and treatment of Crohn’s Disease.

The Phase I study is a double-blind, placebo-controlled, randomised, ascending subcutaneous single dose in healthy volunteers followed by multiple dosing in Crohn’s Disease patients. The study will be conducted in the USA.

Glucagon-like peptide-2 (GLP-2) is a naturally occurring peptide hormone, secreted by the small intestine. GLP-2 binds to and acts exclusively via the GLP-2 receptor, expressed primarily in the gastrointestinal tract. GLP-2 has been shown to have numerous beneficial effects in the small intestine. These include stimulation of the growth of the small intestinal lining, enhancement of nutrient digestion and absorption, and reinforcement of the intestinal barrier function. Moreover, GLP-2 has been shown to decrease inflammation, and to enhance animal survival in a broad range of preclinical models of gut injury including, models of inflammatory bowel disease.

The specific and beneficial actions of GLP-2 in the small intestine makes GLP-2 an attractive therapeutic candidate for the treatment of intestinal injury and/or disease. Nevertheless, GLP-2 is rapidly de-activated in the body (short half-life), representing a significant challenge for the use of GLP-2 clinically. At Zealand Pharma we have applied our knowledge of peptide stabilisation and our technology to produce a novel GLP-2 agonist, ZP1848. ZP1848 is a biologically stable and potent GLP-2 agonist targeted for the treatment of Crohn’s Disease. We have demonstrated that ZP1848 enhances the regeneration of the intestinal lining leading to increased animal well-being and survival in well-validated models of IBD.

ZP1848 is expected to induce and maintain remission by enhancing the regeneration and healing of the small intestinal lining after an inflammatory episode in Crohn’s Disease. This is a novel, innovative and promising therapeutic approach in the treatment of Crohn’s Disease.

ZP1848 has been tested in an extensive preclinical toxicology and safety pharmacology program. In December 2008 an IND was submitted to and approved by the FDA. Zealand Pharma is currently running a Phase I trial to assess the safety and tolerability of ZP1848 in healthy volunteers and Crohn’s Disease patients. Future plans include the testing of ZP1848 in ulcerative colitis enhancer and we believe that ZP1848 is a promising drug candidate for the treatment of inflammatory bowel disease.

Crohn’s Disease

Crohn’s Disease is a chronic, episodic, inflammatory condition of the gastro-intestinal tract characterized by inflammation and transmural lesions (affecting the entire wall of the involved bowel). The other well known IBD is ulcerative colitis, which differs from Crohn’s Disease based on the localisation of the disease and its specific pathologies.

The aetiology of Crohn’s Disease is unknown but involves immune, genetic, and environmental factors. The most common symptoms of Crohn’s Disease include abdominal pain, cramping, fatigue and diarrhoea. Crohn’s Disease can also cause complications outside of the gastrointestinal tract such as skin rashes, arthritis, and inflammation of the eye. The primary goal of treatment in Crohn’s Disease is to suppress and modulate the inflammatory reaction. To achieve this goal anti-inflammatory drugs are used. Nevertheless, the use of these therapeutics is associated with significant drawbacks such as serious side effects, frequent dosing and lack of therapeutic efficacy.

Approximately 700,000 people in the leading seven industrialised countries lived with Crohn’s Disease in 2006 and the incidence of the disease is on the rise in industrialised societies.

For more details, see: www.zealandpharma.com