Gattex may represent new treatment approach for short bowel syndrome

NPS Pharmaceuticals, Inc.May 22 2012

NPS Pharmaceuticals, Inc. (NASDAQ: NPSP), a specialty pharmaceutical company developing innovative therapeutics for rare gastrointestinal and endocrine disorders, today reported the presentation of data at the Digestive Disease Week® (DDW®) meeting held May 19-22 in San Diego. In a poster session, investigators presented data that continue to support Gattex® (teduglutide) as a potential first-in-class treatment for short bowel syndrome (SBS), a rare and debilitating condition in which the body is unable to absorb enough nutrients and/or fluids through the gastrointestinal tract. Patients with SBS depend on chronic parenteral nutrition (PN) and/or intravenous (IV) fluids to survive.    

Investigators reported the baseline characteristics of seven patients with short bowel syndrome who successfully achieved complete independence from PN and IV fluids while on Gattex therapy. In addition, new findings demonstrated that the pharmacological properties of Gattex are associated with significant increases in citrulline, an endogenous non-protein amino acid, that is an indirect measure of enterocyte intestinal mass. In a third presentation, results from a randomized study showed that Gattex does not affect gastric emptying in healthy volunteers.

"Gattex may represent an entirely new approach for treating adult short bowel syndrome and these presentations from multiple clinical studies reinforce our belief in the drug's therapeutic potential," said Roger Garceau, MD, senior vice president and chief medical officer of NPS Pharmaceuticals, Inc. "These data show continued reductions, and for some complete independence from parenteral nutrition (PN) with long-term Gattex therapy, which is encouraging given the serious complications associated with PN."

The following summarizes the three posters presented at DDW:

Abstract Sa1962: "Short Bowel Syndrome Patients with Intestinal Failure (SBS-IF) Successfully Achieved Complete Independence from Parenteral Nutrition" by Jeppesen et al.

In Phase 3 studies, Gattex was shown to significantly reduce PN/IV fluid dependence in patients with SBS with some patients achieving complete independence. In this research, Dr. Jeppesen and colleagues described the characteristics of seven patients who achieved complete independence with Gattex therapy during two Phase 3 placebo-controlled studies and the open-label extension phase of those trials.

The data showed that of 173 patients who received Gattex:

• Three patients achieved independence during the randomized, double-blind phase of Study CL0600-004, of which two patients received 0.05 mg/kg/day Gattex and one patient received 0.10 mg/kg/day Gattex.
• One patient achieved independence during the extension phase of Study CL0600-004.
• Three patients achieved independence during the extension phase of STEPS, the company's 24-week, placebo-controlled Phase 3 registration study.
• Patients were weaned from PN/IV fluid as early as 12 weeks and as late as 52 weeks after initiation of Gattex, suggesting that long-term Gattex use is associated with continued reduction of PN/IV fluid requirements.
• Baseline demographics and disease characteristics were highly variable and the adverse event profile was similar to the overall study population with the most frequently reported adverse events being gastrointestinal related.

Abstract Sa1961: "Teduglutide, a Human Recombinant Analog of Glucagon-Like Peptide-2 (GLP-2), Increases Plasma Citrulline Levels in Patients with Short Bowel Syndrome" by Messing et al.

In this research, Dr. Messing and colleagues assessed changes in plasma citrulline at Week 24 in two double-blind, randomized, placebo-controlled Phase 3 studies of Gattex in short bowel syndrome and showed that in both studies, the mean increase in plasma citrulline at Week 24 vs. baseline was significantly greater in patients receiving Gattex compared with those receiving placebo. Plasma citrulline, an amino acid produced by enterocytes has been considered an indirect measure of remnant enterocyte mass. Gattex has been show to promote expansion of normal intestinal epithelium and increase enterocyte mass by increasing villus height and crypt depth in the small bowel mucosa, leading to increased absorptive area. Mean changes in plasma citrulline levels from baseline occurred early in the course of treatment, with increases as early as Week 4. Patients receiving placebo had minimal changes from baseline in plasma citrulline levels.

Abstract Sa1959: "A Randomized, Double-Blind, Placebo-Controlled, Multiple-Dose, Parallel-Group Study to Assess the Effects of Teduglutide on Gastric Emptying in Healthy Subjects" by Berg et al.

Dr. Berg and colleagues reported results from a double-blind, single-center study that assessed the effect of Gattex on gastric emptying in healthy subjects, and showed that Gattex did not affect gastric emptying in healthy subjects as measured by acetaminophen pharmacokinetics. Gattex did not exert any clinical meaningful effects on serum insulin, glucagon or glucose and there were no clinically significant differences with Gattex between fasted and fed states.