Project: Long Acting Treatment of Inflammatory Bowel Disease

The consortium, StratoSpheres Pharma (StratoSphere) and Zealand Pharma (Zealand), wish to investigate and develop a controlled release GLP-2 drug product for long term treatment of patients suffering from Inflammatory Bowel Disease (IBD). _x000D__x000D_Inflammatory bowel disease (IBD) is a chronic gastrointestinal disorder characterized by unpredictable relapsing inflammation of the intestine, followed by spontaneous remission. IBD embraces two distinct conditions: ulcerative colitis (UC) and Crohn’s disease (CD) distinguished by the location and extent of the intestine inflammation. Approximately 2.2 million persons in the United States and Europe are affected by IBD. At present there is no cure for IBD. Current medical treatment of UC and CD focus on symptoms relieving and induction and COtenance of remission, as well as limitation of side effects of medication and avoidance of complications. The treatment primarily targets inflammation and are associated with significant side effects, frequent dosing and high costs. Moreover, many patients experience that the treatment looses effect over time. Due to these therapeutic shortcomings there is a significant unmet need for novel therapeutic approaches in the treatment of IBD._x000D__x000D_Zealand has developed new peptide GLP-2 receptor agonists with significantly increased biological half-life, increased stability and specificity for the small intestines. StratoSphere has developed a new and gentle process for efficient incapsulation of peptides and proteins into solid but flexible microspheres (Stratospheres HL®) that upon s.c. or i.m. injection forms depots with controlled, long acting release profiles in the range from 1 week to several months duration._x000D__x000D_Crohn's Disease (CD) is a chronic, non-curable, episodic, inflammatory condition of the gastro-intestinal tract characterized by transmural inflammation (affecting the entire wall of the involved bowel) and skip lesions (areas of inflammation with areas of normal lining in between). CD can affect any part of the gastrointestinal tract from mouth to anus, thus, the symptoms of CD are very variable from one patient to the other. The primary gastrointestinal symptoms are abdominal pain, diarrhea, which may be bloody, and weight loss. Moreover, many patients suffer from intestinal obstruction, abscesses and fistulas._x000D__x000D_There is no known medical or surgical cure for Crohn's Disease. The medical treatments applied are aiming at induction and COtenance of remission of the disease. The tratments include high-dose corticosteroid, traditional immunomodulators (e.g. azathioprine and methotrexate), anti-inflammatory medication, Biological Immunomodulators (e.g. Remicade®). All available treatment regimes are associated with suboptimal efficacy and serious side-effects. Tratment with corticosteroids often induce remission but do not alter the overall course of the disease and COtenance therapy with corticosteroids should be avoided due to their side effects. The traditional immunomodulators azathioprine and methotrexate heal the mucosa but their onset of action is slow. Remicade® therapy introduces rapid mucosal healing, but 60% of treated patients have lost response at week 54. Improvement of symptoms is no longer satisfactory and modification of the clinical course of the disease has become the major goal._x000D__x000D_As the clinical symptoms of IBD reflect superficial mucosal inflammation, treatments that induce healing/growth of the intestinal mucosa may provide particular clinical benefits. If a treatment induces profound and long-lasting mucosal healing, it may reduce complications including need for surgical interventions and therefore such a drug could potentially slow down or even stop the progression of the disease. The Zealand Pharma compound ZP1848 is a Mucosal Regeneration Enhancer that represents a new class of therapeutic compounds in the treatment of IBD. The significant unmet medical need for effective and safe therapies makes the commercial potential very attractive. _x000D__x000D_Very few protein and peptide drug delivery systems for controlled release have been developed and launched over the years. Most often problems with degradation of the drug in the manufacturing process or during storage, and problems with initial high burst of the active drug has been the reason for lack of success._x000D__x000D_By combining the technologies of the two companies, the consortium seek to develop depot formulation of the active compound to improved efficacy and patient compliance and to achieve retained biological activity and significantly improved pharmaco-dynamic profile. _x000D_

Acronym LATIBD (Reference Number: 5304)
Duration 04/01/2010 - 30/08/2011
Project Topic Zealand Pharma has experience in development of peptide therapeutics with activity in inflammatory bowel diseases.Stratosphere Pharma has experience in controlled release delivery systems for peptides and proteins.The two companies want to combine their expertice to develop an improved drug product.
Project Results
(after finalisation)
The development of a depot product of ZP1848 was only partially successful in that satisfactory release profiles of the drug from the formulation could be obtained in vitro, but the in vivo release, as determined by concentration in the blood over time, was too low. This is most likely caused by a strong interaction of the drug with hyaluronic acid in the subcutaneous environment, which with the designed low release rates from the microcapsules results in a too high binding in the tissue.
Network Eurostars
Call Eurostars Cut-Off 3

Project partner

Number Name Role Country
2 Zealand Pharma A/S Coordinator Denmark
2 StratoSphere Pharma AB Partner Sweden