Tranzyme Pharma, a leading biopharmaceutical company developing small molecule therapeutics for the treatment of gastrointestinal (GI) disorders, presented positive data highlighting the effectiveness of its TZP-101 in promoting gastrointestinal (GI) motility in animal models of post-operative ileus (POI).
The data was presented by scientists from the University of Oklahoma and Tranzyme Pharma at the Digestive Disease Week 2005 Conference (Chicago, IL).
TZP-101 is a novel small molecule ghrelin agonist being developed by Tranzyme Pharma as a first-in-class treatment for both POI and diabetic gastroparesis, serious medical conditions in which motility of the GI tract is severely impaired.
Dr Beverly Greenwood-Van Meerveld, a leading GI researcher at the University of Oklahoma Health Sciences Centre, presented the results of her studies utilizing a validated rat model of POI.
The data demonstrate that TZP-101 induced a dose-dependent increase of gastric emptying that effectively reversed the delay caused by surgically induced POI. Treatment levels as low as 30µg/kg were shown to be effective in stimulating GI transit in this model. Furthermore, TZP-101 significantly stimulated gastric emptying in naïve rats with 100-fold greater potency than metoclopramide, a compound currently marketed as a prokinetic treatment for gastroparesis.
"I am impressed with the results of this proof-of-concept study. POI is one
example of a GI motility disorder where a new class of gastroprokinetic agent, such as TZP-101, may offer great therapeutic potential," stated Dr Greenwood-Van Meerveld.
In a separate presentation by Graeme L Fraser, vice president of Drug Discovery for Tranzyme Pharma, TZP-101 shows highly favourable pharmacokinetic profile including excellent oral availability.
"These are exciting preclinical results that independently confirm the efficacy of TZP-101," said Vipin K Garg, president & CEO for Tranzyme Pharma.
"Our development programme remains on track to file an IND for TZP-101 for POI by Q4 2005. The goal is to initiate Phase I clinical trials for this indication by the end of 2005, followed shortly thereafter by Phase I trials for diabetic gastroparesis," Garg added.
POI is an impairment of gastrointestinal motility that is an inevitable consequence of major abdominal surgery, especially under conditions of bowel resection. POI has an annual economic impact of $1.75 billion. There are no FDA-approved products for the treatment of POI. Diabetic gastroparesis is the impairment of stomach motility observed in both Type I and Type II diabetics to the extent that up to 10 per cent of these patients require hospitalization at some stage for nausea, vomiting abdominal pain and malnutrition.
Existing therapies for this condition offer poor efficacy and/or severe side effects. Moreover, the two most popular products for the treatment of
gastroparesis (cisapride and domperidone) have been removed from the US market due to their adverse side effects.
Ghrelin is the most potent endogenous peptide known to stimulate gastric motility. Recent independent clinical studies have clearly demonstrated that infused ghrelin peptide potently stimulates gastric emptying in both human volunteers and diabetic gastroparesis patients. However, the ghrelin peptide has limited utility as a therapeutic product for GI indications due to its brief pharmacokinetic half-life and poor oral bioavailability, problems overcome by TZP-101.