NPS Pharmaceuticals Inc., a specialty pharmaceutical company developing orphan therapeutics for rare gastrointestinal and endocrine disorders, announced that it has submitted the chemistry, manufacturing and controls (CMC) section of its New Drug Application (NDA) for Gattex (teduglutide) to the US Food and Drug Administration (FDA).

Gattex is a novel, recombinant analogue of human glucagon-like peptide 2 that the company is developing for the treatment of adults with short bowel syndrome or SBS. SBS is a highly disabling disorder in which the body is unable to absorb sufficient nutrients and/or fluids through the gastrointestinal tract. Patients with SBS often rely on parenteral nutrition (PN) or intravenous (IV) fluids to survive.

“This rolling submission is an important milestone for NPS and brings us one step closer to commercializing Gattex,” said Francois Nader, MD, president and chief executive officer of NPS Pharmaceuticals. “We believe Gattex represents an important treatment advance for patients with short bowel syndrome, and we look forward to submitting the remainder of our US marketing application later this year.”

FDA regulations permit an applicant to submit the CMC section 90 to 120 days before the anticipated submission of the remainder of the application. FDA will review the early CMC submission as resources permit.

Earlier this year, NPS reported positive data from a 24-week phase III pivotal study of Gattex. The study, known as STEPS, evaluated the ability of Gattex to reduce PN and IV fluid requirements of adult subjects with SBS. The primary efficacy endpoint was defined as the percentage of patients who achieved a 20 to 100 per cent reduction in weekly PN/IV volume at Weeks 20 and 24, compared to baseline. In the intent-to-treat population, 63 percent (27/43) of Gattex-treated patients were responders versus 30 percent (13 of 43) of placebo-treated patients (p=0.002).

Subjects treated with Gattex for 24 weeks achieved significantly greater reductions in weekly PN and IV fluid volume and infusion days versus placebo. At Week 24, subjects who received Gattex experienced an average 4.4 liter reduction in weekly PN/IV volume from a pre-treatment baseline of 12.9 liters; subjects who received placebo experienced an average 2.3 liter reduction from a pre-treatment baseline of 13.2 liters (pless-than or equal to 0.001). After completing 24 weeks of treatment, 54 percent (21 of 39) of Gattex-treated subjects were able to reduce the number of infusion days per week by one or more days, compared to 23 percent (9 of 39) of those treated with placebo (p=0.005).

The company is also advancing STEPS 2, an open-label continuation study of STEPS in which each subject receives Gattex. At an interim update in May 2011, NPS reported that three subjects participating in STEPS 2 were able to gain independence from and discontinue PN and IV fluids.

The lead indication for Gattex is treatment of adults with short bowel syndrome. NPS has reported findings from completed studies in which Gattex was well tolerated and effectively reduced parenteral nutrition and intravenous fluid volume requirements in subjects with adult short bowel syndrome.

Teduglutide has received orphan drug designation for the treatment of SBS from the US Food and Drug Administration and the European Medicines Agency.

In March 2011, Nycomed submitted a Marketing Authorization Application (MAA) to the European Medicines Agency (EMA) for clearance to market teduglutide (Revestive) as a once-daily subcutaneous treatment for short bowel syndrome. 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.

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 or intravenous fluids (parenteral support) to supplement and stabilize nutritional needs.

Although parenteral support can meet basic nutrition and fluid requirements by delivering them intravenously, it does not improve the body's own ability to absorb nutrients. Parenteral support is also associated with serious complications, such as infections, blood clots or liver damage, and the risks increase the longer patients are on it. Patients on parenteral support 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 US who are dependent on parenteral support, the direct cost of which can exceed $ 100,000 annually per patient.