New Findings Demonstrate Potential Benefits of GATTEX (teduglutide) in Phase 3 Study of Patients with Short Bowel Syndrome
Presentations at DDW Show GATTEX™ Enhances Intestinal Mass and Function
BEDMINSTER, N.J. & CHICAGO--(BUSINESS WIRE)--Jun 3, 2009 - Clinical investigators presented new data from three sub-studies in patients with short bowel syndrome (SBS) who received GATTEX™ (teduglutide) during a 24-week, placebo-controlled Phase 3 clinical trial. Results were presented at the annual Digestive Disease Week (DDW) Congress taking place in Chicago.
Investigators reported that teduglutide achieved a significant increase in absolute intestinal absorption and a decrease in electrolyte losses in SBS patients dependent on parenteral nutrition (PN), with no significant changes observed from baseline for placebo. In addition, new findings demonstrated changes in citrulline, an endogenous non-protein amino acid, appear to be useful biomarkers of PN reduction response when teduglutide is used. Data also suggest that patients with an increase in citrulline at week eight are likely to achieve a significant response, as defined by a greater than 20% reduction in PN. In the third sub-study, investigators reported that with a constant dietary intake, 24 weeks of teduglutide treatment significantly increased energy absorption in PN-dependent SBS patients. GATTEX™ (teduglutide) is a novel investigational compound that may reduce dependence upon PN in patients with SBS, a rare disorder primarily caused by intestinal resection and the subsequent inability to maintain oral fluid, electrolyte, and nutrient balances.
Abstract 897: “Teduglutide, a Novel GLP-2 Analogue, Decreases Fecal Wet Weight, Sodium and Potassium Excretion in Short Bowel Syndrome (SBS) Patients Dependent on Parenteral Nutrition (PN)” by P. Jeppesen et al.
To quantify the ability of teduglutide to increase absorption, decrease fecal wet weight and decrease electrolyte losses Palle B. Jeppesen, M.D., and colleagues conducted a 72-hour balance sub-study. Twenty-one patients on a standardized diet were included and complete data were obtained from 14 of the 21 patients (3 placebo and 11 teduglutide).
With teduglutide, fecal wet weight decreased by 735±574 grams per day at week 24 as compared to baseline (p=0.006). Absolute intestinal absorption, calculated as the weight difference between oral intake and fecal excretion, increased by 795±618 grams per day at week 24. In addition teduglutide decreased electrolyte losses, with decreases in fecal sodium and potassium of 49±30 (p<0.001) and 19±22 (p=0.003) millimoles per liter per day, respectively. Investigators did not observe any significant changes from baseline for placebo.
Abstract 898: “Citrulline: a Potential Predictor of Reductions in Parenteral Nutrition Achieved in Chronic Parenteral Nutrition Dependant Patients with Short Bowel Syndrome (SBS) Treated with Teduglutide” by R. Gilroy et al.
Richard Gilroy, M.D., and colleagues presented results of a sub-study exploring whether changes in citrulline predict reductions in PN in patients receiving 0.05 mg/kg/day of teduglutide, a dose associated with significantly higher response rates when compared to placebo. A clinically significant PN response was defined as a weekly reduction of PN requirements of more than 20% at dosing week 20 and maintained through dosing week 24. In an intent-to-treat analysis 16 of 35 patients (46%) treated for 24 weeks demonstrated a response versus one of 16 in the placebo arm (p=0.007). In this sub-study, investigators examined citrulline, a biomarker of intestinal mass, in the population of patients who had achieved a significant clinical response to see if changes in this biomarker predicted reductions in PN. In this study, there was a correlation between increases in citrulline and reductions in PN. This supports a role for citrulline as a predictor for reducing PN through teduglutide use in SBS patients.
Abstract T1281: “The Influence of Teduglutide, a Novel GLP-2 Analogue, on Energy Absorption in Short Bowel Syndrome (SBS) Patients Dependent on Parenteral Nutrition (PN)” by P. Jeppesen et al.
To quantify the ability of teduglutide to increase energy absorption, Dr. Jeppesen and colleagues conducted a 72-hour balance sub-study. Twenty-one patients on a standardized diet were reviewed. Investigators calculated absolute energy absorption and relative energy absorption at baseline, week 8, and week 24. Complete data were obtained from 14 of the 21 patients (3 placebo and 11 teduglutide). For those patients who were treated with teduglutide whose dietary energy content did not differ by more than 10% from baseline values (n=6), fecal energy excretion decreased and intestinal absorption increased significantly (p<0.05) at week 8 and at week 24 compared to baseline. Investigators concluded that with a constant dietary intake, six months of teduglutide treatment significantly increased energy absorption in PN-dependent SBS patients.
About GATTEX™ (teduglutide)
GATTEX is a proprietary analog of human glucagon-like peptide 2 that stimulates the repair and regeneration of cells lining the intestine. Patient enrollment is underway in a Phase 3 registration study to confirm previously reported data that demonstrated GATTEX was well tolerated and reduced parenteral nutrition (PN) dependence in short bowel syndrome patients. The international, double-blind, placebo-controlled safety and efficacy study of GATTEX is known as STEPS (Study of TEduglutide in PN-dependent Short-bowel syndrome). More information on STEPS, can be found at http://clinicaltrials.gov.
NPS is also advancing preclinical studies to evaluate teduglutide in additional intestinal failure related conditions.
Teduglutide is currently under investigation for 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. FDA and the European Medicines Agency. NPS's partner, Nycomed, is responsible for European development and commercialization.
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.
DDW is the largest international gathering of physicians, researchers and academics in the fields of gastroenterology, hepatology, endoscopy and gastrointestinal surgery. Jointly sponsored by the American Association for the Study of Liver Diseases, the AGA Institute, the American Society for Gastrointestinal Endoscopy and the Society for Surgery of the Alimentary Tract, DDW is taking place May 30 - June 4, 2009, at the McCormick Place Convention Center. The meeting showcases approximately 5,000 abstracts and hundreds of lectures on the latest advances in GI research, medicine and technology. For more information, visit www.ddw.org.
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 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: June 2009