NPS Pharmaceuticals, Inc., a specialty pharmaceutical company developing innovative therapeutics for rare gastrointestinal and endocrine disorders, today announced that its Phase 3 pivotal study of GATTEX® (teduglutide) met the primary efficacy endpoint of reducing parenteral nutrition (PN) dependence in patients with adult short bowel syndrome (SBS). The 24-week randomized, double-blind study, known as STEPS, was designed to compare the efficacy, safety and tolerability of GATTEX to placebo.
The study reached statistical significance for the primary efficacy endpoint, defined as the percentage of patients who achieved a 20 percent or greater reduction in weekly PN volume at Weeks 20 and 24, compared to baseline. In an intent-to-treat analysis, 63 percent (27/43) of GATTEX-treated patients responded versus 30 percent (13/43) of placebo-treated patients.
"SBS patients who receive their nutrients and fluids intravenously due to malabsorption and diarrhea are prone to a number of serious complications including life-threatening infections, blood clots and liver and kidney damage. The STEPS results suggest teduglutide helps restore normal intestinal function in patients with short bowel syndrome, thereby reducing dependence on parenteral nutrition and potentially improving their quality of life," said Palle Bekker Jeppesen, M.D., associate professor, department of medical gastroenterology, Rigshospitalet, University Hospital of Copenhagen, Denmark. "These findings bring us closer to an important new therapeutic option for patients with this debilitating condition."
The STEPS study showed that GATTEX was well tolerated. Four of the 86 randomized patients discontinued the study due to adverse events, of which one was GATTEX-treated and three were placebo-treated. Adverse events appear to be consistent with the pharmacological effects of the drug.
"We are very pleased with these findings as they confirm our belief that GATTEX provides meaningful clinical benefits to adult patients with short bowel syndrome," said Francois Nader, MD, president and chief executive officer of NPS Pharmaceuticals. "Based on these results, we expect to file for FDA approval of GATTEX in the second half of this year as a first-in-class treatment for SBS. We thank the patients, clinical investigators, and study coordinators who participated in this landmark study, as well as our ex-North American partner Nycomed who co-managed and co-funded the study. We look forward to reporting additional results from the STEPS study at upcoming medical meetings."
More than 97 percent of eligible patients who participated in STEPS elected to roll into STEPS 2, an open-label continuation study in which all participants receive up to an additional 24 months of GATTEX therapy.
STEPS study design
STEPS was an international, double-blind, placebo-controlled Phase 3 pivotal study designed to provide additional evidence of safety and efficacy of GATTEX in reducing PN dependence in adult SBS patients.
Twenty-nine centers in North America and Europe enrolled patients in the STEPS study. Eighty-six patients were randomized and analyzed for efficacy and safety. The trial included an initial PN optimization and stabilization period, after which patients were randomized 1:1 to compare daily subcutaneous dosing of 0.05 mg/kg of GATTEX to placebo over a 24-week treatment period. A total of 78 patients completed the study.
The primary efficacy endpoint was the percentage of patients who achieved a 20 percent or greater reduction in weekly PN volume at Week 20 and maintained that response at Week 24, compared to baseline. The study's secondary endpoints included reductions in PN volume and the direct effects of improved intestinal absorption of fluid.
NPS conducted STEPS with the support of its partner, Nycomed, a global pharmaceutical company, headquartered in Switzerland, which holds the rights to develop and commercialize teduglutide outside of North America. Nycomed expects to submit a Marketing Authorization Application (MAA) to the European Medicines Agency (EMA) for teduglutide in the first half of 2011. The two companies share certain external costs for the teduglutide development program.