Data Demonstrate That GATTEX(Teduglutide) Improves Lean Body Mass, Mineral Composition and Electrolyte Levels in Patients with Parenteral Nutrition Dependent Short Bowel Syndrome
Additional Data from Phase 3 Study Presented at the American College of Gastroenterology (ACG) Meeting
BEDMINSTER, N.J. & SAN DIEGO--(BUSINESS WIRE)--Oct 26, 2009 - NPS Pharmaceuticals, Inc. (NASDAQ:NPSP) today reported additional data from a Phase 3 study supporting the efficacy of GATTEX™ (teduglutide) in patients with parenteral nutrition (PN)-dependent short bowel syndrome (SBS). Data were presented at the American College of Gastroenterology (ACG) 2009 Annual Scientific Meeting and Postgraduate Course taking place in San Diego, October 23-28.
Data from the randomized, placebo-controlled, 24-week study showed that teduglutide significantly improved lean body mass and total bone mineral content in PN-dependent SBS patients (Abstract P272). A separate presentation showed that teduglutide improves intestinal electrolyte and wet weight absorption in SBS patients (Abstract P273). Previously reported results from the study showed that teduglutide was generally well-tolerated and effective in reducing the PN requirements of SBS patients.
“PN-dependent SBS patients are prone to a number of serious complications including malnutrition, dehydration and osteoporosis, so it is very encouraging to see that teduglutide significantly improved patients' ability to absorb nutrients, gain lean body mass and more effectively maintain mineral levels required for healthy bones,” said Palle Bekker Jeppesen, M.D., lead author of both studies and Associate Professor, Department of Medical Gastroenterology University Hospital of Copenhagen. “We look forward to completing and seeing the results of a second Phase 3 study, which is presently underway. That study could confirm prior findings suggesting that teduglutide reduces the need for intravenous feeding and potentially enhances the quality of lives of SBS patients.”
The 83 patients in the Phase 3 study all had SBS resulting from major intestinal resection and required PN infusions three or more times per week. Following a 4-16 week optimization and stabilization period, patients were randomized to placebo or one of two dose levels of teduglutide (0.05 or 0.10 mg/kg/d sc) for 24 weeks. PN fluid volume was weaned according to an algorithm based on changes in urine production in relation to teduglutide treatment.
Abstract P272: “Teduglutide (TG), a Dipeptidyl-peptidase IV Resistant Glucagon-like Peptide 2 (GLP-2) Analogue, Improves Lean Body Mass and Total Mineral Content in Short Bowel Syndrome (SBS) Patients Depending on Home Parenteral Nutrition (PN). Dual Energy X-ray Absorptiometry (DEXA) Results from a Randomized, Placebo-controlled, 24-week Study” by P. Jeppesen et al.
In this study, investigators performed Dual Energy X-ray Absortiometry (DEXA) scans of all the patients prior to dosing to compare body composition (total body bone mineral content, fat and lean body mass) at baseline to body composition at the conclusion of the 24-week dosing cycle. The DEXA scans revealed significant improvements in lean body mass and mineral content in patients who received teduglutide compared to those who received placebo. Jeppessen and colleagues concluded the increase in lean body mass may be related to teduglutide-induced improvements in intestinal energy and/or fluid absorption, whereas the improved mineral content may be related to reductions in bone resorption. These effects of teduglutide are desirable in PN-dependent SBS patients, as they are prone to malnutrition, dehydration and osteoporosis.
Abstract P273: “Teduglutide (TG) Improves Electrolyte and Wet Weight Absorption in Short Bowel Syndrome Patients, but this is not correlated to increases in Plasma Citrulline (PC)” by P. Jeppesen et al.
This study was designed to measure the effectiveness of using plasma citrulline (PC) as a biomarker of gut function. In this study, teduglutide increased intestinal wet weight and sodium absorption in SBS patients. Although this was accompanied by an increase in PC, there was no significant correlation between these improvements. Jeppesen and colleagues concluded that while PC may be a surrogate marker of remaining intestinal absorptive cells in SBS patients, balance studies seem to remain the gold standard for measuring intestinal function.
Phase 3 Confirmatory Study
Patient enrollment is ongoing in a second Phase 3 study known as STEPS (Study of TEduglutide in PN-dependent Short-bowel syndrome). STEPS is an international, double-blind, placebo-controlled study to confirm that teduglutide is well tolerated and reduces parenteral nutrition (PN) dependence in short bowel syndrome (SBS) patients. NPS expects STEPS to complete enrollment before the end of the first quarter of 2010.
STEPS will compare daily subcutaneous dosing of 0.05 mg/kg of teduglutide to placebo over a 24-week treatment period. After completing 24-weeks, patients will be offered the option to enter an open-label extension phase (STEPS 2) for up to an additional 24 months, in which patients previously treated with teduglutide or placebo will receive teduglutide.
NPS is advancing STEPS with the support of its partner, Nycomed. In 2007, NPS granted Nycomed the rights to develop and commercialize teduglutide outside the United States, Canada and Mexico. NPS retains all North American rights.
NPS believes positive results from STEPS will enable it to seek U.S. marketing approval for GATTEX for patients with PN-dependent SBS.
For more information on STEPS, please contact NPS or visit http://www.npsp.com or http://clinicaltrials.gov/ct2/show/NCT00798967?term=teduglutide&rank=2.
About GATTEX™ (teduglutide)
GATTEX is the brand name for teduglutide, a proprietary analog of naturally occurring human glucagon-like peptide 2 (GLP-2), a peptide secreted primarily in the distal intestine and involved in the regeneration and repair of the intestinal epithelium. Preclinical and clinical studies have demonstrated that GATTEX stimulates the repair and regeneration of cells lining the small intestine, expanding the surface area for absorption of nutrients. Given teduglutide's mechanism of action to promote gastrointestinal repair, NPS believes it has the potential to treat gastrointestinal conditions associated with intestinal failure. Teduglutide is currently under investigation for short bowel syndrome (SBS) and has not been approved for marketing by the U.S. Food and Drug Administration (FDA). Teduglutide has received orphan drug designation for the treatment of SBS from the U.S. Food and Drug Administration and the European Medicines Agency.
NPS is developing GATTEX in North America and has licensed to Nycomed the right to develop and commercialize GATTEX in all other regions. Nycomed and NPS are collaborating on the development of teduglutide for the treatment of gastrointestinal disorders.
About Short Bowel Syndrome (SBS)
SBS is a highly disabling condition that impairs quality of life and can lead to serious life-threatening complications. SBS typically arises after extensive resection of the bowel. There are an estimated 10,000 to 15,000 SBS patients in North America who are dependent on parenteral nutrition (PN), the cost of which can exceed $100,000 annually per patient. SBS patients suffer from malnutrition, severe diarrhea, dehydration, fatigue, osteopenia, and weight loss due to an inability to absorb adequate amounts of nutrients, fluid, and electrolytes. The goals of current treatment are to maintain fluid, electrolytes and nutrient balances through dietary management, including the use of PN. Long-term complications of the condition may include an increased risk of systemic infections due to the presence of an intravenous feeding line, degenerative changes in the bones and nerves due to vitamin and mineral deficiencies, and liver failure. Potential benefits derived from reduced dependence on PN may include improved nutrition and hydration, lower rates of infections, and improved quality of life due to more time away from PN, which may provide greater mobility and improved sleep.
About NPS Pharmaceuticals
NPS Pharmaceuticals is developing new treatment options for patients with rare gastrointestinal and endocrine disorders. The company is currently conducting two Phase 3 registration studies. Teduglutide, a proprietary analog of GLP-2, is being evaluated as GATTEX™ in a Phase 3 registration study known as STEPS for intestinal failure associated with short bowel syndrome and in preclinical development for chemotherapy-induced gastrointestinal mucositis, as well as potential pediatric indications. NPSP558 (parathyroid hormone 1-84 [rDNA origin] injection) is being evaluated in a Phase 3 registration study known as REPLACE as a hormone replacement therapy for hypoparathyroidism. NPS complements its proprietary programs with a royalty-based portfolio of products and product candidates that includes agreements with Amgen, GlaxoSmithKline, Kyowa Kirin, Nycomed, and Ortho-McNeil. Additional information is available at http://www.npsp.com.
“NPS” and “NPS Pharmaceuticals” are the company's registered trademarks. All other trademarks, trade names or service marks appearing in this press release are the property of their respective owners.
Statements made in this press release, which are not historical in nature, constitute forward-looking statements for purposes of the safe harbor provided by the Private Securities Litigation Reform Act of 1995. These statements are based on the company's current expectations and beliefs and are subject to a number of factors and uncertainties that could cause actual results to differ materially from those described in the forward looking statements. Risks associated to the company's business include, but are not limited to, the risks associated with any failure by the company to successfully complete its preclinical and clinical studies within the projected time frames or not at all, the risk of not gaining marketing approvals for GATTEX and NPSP558, the risks associated with the company's strategy, the risks associated with the company's auction-rate securities, as well as other risk factors described in the company's periodic filings with the U.S. Securities and Exchange Commission, including its Annual Report on Form 10-K and Form 10-Qs. All information in this press release is as of the date of this release and NPS undertakes no duty to update this information.
Posted: October 2009