NPS Pharmaceuticals, Inc. a specialty pharmaceutical company developing innovative therapeutics for rare gastrointestinal and endocrine disorders, announced that its phase III 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 (p=0.002).
Patients treated with Gattex for 24 weeks also achieved significantly greater reductions in weekly PN volume versus placebo. On average, patients who received Gattex experienced a 4.4 litre reduction in weekly PN volume from a pre-treatment baseline of 12.9 litres; patients who received placebo experienced a 2.3 litre reduction from a pre-treatment baseline of 13.2 litres (p less than or equal to 0.001).
“SBS patients who receive their nutrients and fluids intravenously due to mal-absorption and diarrhoea 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, MD, 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 was an international, double-blind, placebo-controlled phase III pivotal study designed to provide additional evidence of safety and efficacy of Gattex in reducing PN dependence in adult SBS patients.
Twenty-nine centres 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 programme.
Short Bowel Syndrome, or SBS, is a highly disabling condition that can impair a patient's quality-of-life and lead to serious life-threatening complications. SBS typically arises after extensive resection of the bowel due to Crohn's disease, ischemia or other conditions. SBS patients often suffer from malnutrition, severe diarrhoea, dehydration, fatigue, osteopenia, and weight loss due to the reduced intestinal capacity to absorb nutrients, water, and electrolytes. The usual treatment for short bowel syndrome is nutritional support, including Parenteral Nutrition (PN) or intravenous feeding to supplement and stabilize nutritional needs.
Although PN can provide nutritional support for short bowel syndrome patients, it does not improve the body's own ability to absorb nutrients. PN is also associated with serious complications, such as infections, blood clots or liver damage, and the risks increase the longer patients are on PN. Patients on PN often experience a poor quality-of-life with difficulty sleeping, frequent urination and loss of independence.
There are an estimated 10,000 to 15,000 SBS patients in the U.S. who are dependent on PN, the direct cost of which can exceed $100,000 annually per patient.
Gattex (teduglutide) is a novel, recombinant analogue of human glucagon-like peptide 2, a protein involved in the rehabilitation of the intestinal lining. Gattex is in phase III development to reduce dependence on Parenteral Nutrition (PN) in adult patients with SBS. NPS has reported findings from completed studies in which Gattex demonstrated a favourable safety profile and reductions in mean PN volume from pre-treatment baseline were observed. NPS is also advancing preclinical studies to evaluate teduglutide in additional intestinal failure related conditions.
Teduglutide has received orphan drug designation for the treatment of SBS from the US Food and Drug Administration and the European Medicines Agency. In 2007, NPS granted Nycomed the rights to develop and commercialize teduglutide outside the United States, Canada and Mexico. NPS retains all rights to teduglutide in North America.
NPS Pharmaceuticals is developing new treatment options for patients with rare gastrointestinal and endocrine disorders and is currently advancing two phase III registration programmes.