Zealand Pharma A/S (Zealand), a biotech company, informed that it has successfully dosed the first patients in a clinical phase II Proof-of-Concept trial with ZP1848 for the treatment of short bowel syndrome (SBS). SBS is a serious condition of intestinal function failure following surgical removal of large parts of the intestines due to cancer, ischemia or Crohn’s disease. ZP1848 is a novel, long-acting GLP-2 analogue with a unique stability profile in liquid formulation, which is invented and fully owned by Zealand.
GLP-2 based therapy is an established concept in the treatment of SBS, and in preclinical studies, ZP1848 has shown promising effects over existing treatment. The start of patient in the phase II trial is an important step in the further development of ZP1848 in that the trial is intended to demonstrate the clinical relevance and profile of the product as a new and better treatment option.
ZP1848 is the second proprietary medicine Zealand has advanced into clinical phase II development only in 2016. Earlier in February, Zealand informed that it had initiated dosing of patients in a phase II trial with its stable glucagon analogue, ZP4207 for the single-dose rescue treatment of severe hypoglycemia in diabetes. In accordance with its strategic focus, Zealand has thus taken important steps in advancing its proprietary pipeline of peptide-based specialty medicines, which now counts three products in phase II development.
Britt Meelby Jensen, president and CEO at Zealand, said, “I consider ZP1848 an important and very promising product in Zealand’s growing proprietary pipeline of peptide medicines. Patients with short bowel syndrome have high mortality and severely reduced life quality, and we are eager with our phase II trial to hopefully show support for the potential for this long acting GLP-2 as a new and better treatment for these patients.”
She added “This is the second proprietary product that we have advanced into phase II development this month, showing clear progress in the execution of our strategy of growing Zealand’s proprietary pipeline of medicines for accelerated value creation. I am excited about these achievements and I look with strong confidence into 2016, where we expect more significant milestones for our company.”
The phase II Proof-of-Concept trial with ZP1848 is a randomized, double-blind, dose-finding trial to investigate the clinical efficacy and safety of the compound in the treatment of SBS. The trial is conducted at the world-leading gastrointestinal center at the University Hospital of Copenhagen (Rigshospitalet), Denmark, and will enroll 18 patients with SBS. Patients in the trial will be randomized to three dosis groups and treated with two different doses of ZP1848 for a total of six weeks interrupted by a wash-out period. The primary objective of the trial is to assess the effect of ZP1848 on improving patients’ intestinal absorption capacity measured as reduction in fecal wet weight output. In addition, the trial will evaluate a number of relevant secondary efficacy endpoints, including change in urine weight and changes in absorption of electrolytes and macronutrients. Completion of and results from the phase II trial are expected in 2017.
In preclinical studies, ZP1848 has shown to significantly increase small intestine mass compared to a marketed GLP-2 analogue. In addition, the compound has demonstrated important physio-chemical properties of a long-acting, stable and soluble peptide therapeutic, leaving potential for its convenient administration in readily available liquid formulation. Zealand has also investigated ZP1848 in a combined single and multiple ascending dose phase I trial. Results from this trial demonstrated that ZP1848 is safe and well tolerated and has a supportive effect on bowel function.
SBS is a complex chronic disease characterized by severe 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 colon cancer, ischemia, Crohn’s disease and radiation.