January 30, 2013 at 08:00 AM EST
New Peer-reviewed Publication Offers Guidance for Integrating Gattex® (Teduglutide [rDNA origin]) for Injection into Management of Short Bowel Syndrome

The Journal of Parenteral and Enteral Nutrition recently published clinical considerations and best-practice recommendations for introducing Gattex® (teduglutide [rDNA origin]) for injection into the management of short bowel syndrome (SBS). The recommendations conclude that integrating Gattex into a coordinated approach to treating SBS may result in more success in rehabilitating the intestine and weaning from parenteral nutrition (PN)/intravenous (IV) fluids in these patients.

Gattex is indicated for the treatment of adults with SBS who are dependent on parenteral support. Full prescribing information for Gattex is available at www.Gattex.com. The complete guidelines can be viewed at the Journal of Parenteral and Enteral Nutrition website by searching “teduglutide.”

The goal of intestinal rehabilitation is to enhance nutrient processing and absorptive capacity of the remaining gastrointestinal tract, allowing for maximum oral intake of nutrients and fluids. Until recently, the approaches for achieving this goal have been limited to dietary intervention, antidiarrheal and antisecretory medications, and surgical bowel reconstruction. The article considers the integration of Gattex, a targeted agent, in conjunction with best-practice recommendations, including strategies for PN/IV weaning and the importance of an integrated approach centering on specialized care.

“Teduglutide achieves intestinal adaptation as evidenced by significant reductions in PN/IV dependence or even complete weaning of this supportive care in some patients with short bowel syndrome,” said Douglas L. Seidner, MD, director of Vanderbilt Center for Human Nutrition at Vanderbilt Medical Center in Nashville and lead author. “Due to the complexities of short bowel syndrome and the need for individualized management strategies, patients should be referred to major centers with experience in short bowel syndrome, particularly during the early stages of teduglutide treatment.”

Prior to initiating therapy with Gattex, the authors suggest optimizing fluids, electrolytes, nutrients, and adjunctive medications. They also recommend establishing baseline parameters for monitoring purposes, particularly nutrient balance and liver function for those requiring long-term, home use of parenteral nutrition, or HPN. Pre-planning and communication between the various healthcare providers and the patient are strongly recommended to allow for a well-coordinated care plan. Further, the authors recommend that patients be referred to major centers with experience in intestinal rehabilitation and that Gattex prescribers adhere to the warnings and requirements for the specific population of patients described in the product’s label.

These are the first published recommendations for weaning SBS patients off of PN/IV while on Gattex. The recommendations detail that the intended approach to reducing dependence on PN/IV should clearly be determined in the planning stages, prior to initiating therapy with Gattex, citing patient and caregiver preferences. It is also recommended that throughout the weaning process, with or without teduglutide, continued monitoring of key parameters should be tracked closely to ensure safe withdrawal of PN/IV. In addition, it is recommended that patients keep a diary to record oral food and fluid intake, urine output, and stool/stoma characteristics and share it with their prescribing physician. Further, patients should be educated on signs of fluid overload that could arise during the weaning process and advised to report rapid changes in weight and urine output to their prescribing physician.

The guidelines were formed by a panel of experts convened in a roundtable that was sponsored by NPS Pharmaceuticals. In addition to Dr. Seidner, the panel consisted of Lauren K. Schwartz, MD, Marion F. Winkler, PhD, RD, LDN, CNSC, FASPEN, Khursheed Jeejeebhoy, MD, FRCP(C), PhD, Joseph I. Boullata, PharmD, RPh, BCNSP, Kelly A. Tappenden, PhD, RD, FASPEN, and Joan Bishop of The Oley Foundation.

About Short Bowel Syndrome

Short bowel syndrome, or SBS, is a serious, complex disorder in which the body is unable to absorb enough nutrients and fluids through the gastrointestinal tract to sustain life. SBS patients are commonly infused with parenteral nutrition and IV fluids, or parenteral support, five to seven nights per week for up to 10 to 12 hours at a time, and in extreme cases, some patients could receive parenteral support for 24 hours a day. Long-term use of parenteral support can be associated with life-threatening complications such as liver damage, serious bloodstream infections, and blood clots.

SBS typically occurs when a large portion of the intestine has been removed by surgery caused by disease or injury. In rare cases, it is congenital. Common symptoms of SBS can include diarrhea, dehydration, malnutrition, and weight loss, which are closely related to the functional issues of the bowel. During a typical day, SBS patients will move their bowels up to 10 times, or change their ostomy bag, which collects their stool output, three to four times. In extreme cases, patients may move their bowels as many as 25 times each day.

Gattex Clinical Trials

NPS' clinical development program for Gattex is the largest and most comprehensive conducted in SBS patients to date, consisting of 15 clinical studies. Across all clinical studies, 566 subjects were exposed to at least one dose of Gattex, of whom 134 had SBS and were treated with 0.05 mg/kg/day Gattex. The FDA's approval of Gattex was based on an international, 24-week, double-blind, placebo-controlled, pivotal Phase 3 trial, known as STEPS. The primary endpoint of STEPS was defined as a 20 percent or greater PN/IV volume reduction demonstrated at week 20 and sustained at week 24. The study's secondary endpoints included reductions in PN/IV volume and additional days off therapy. Key findings from the STEPS trial include:

  • In an intent-to-treat analysis at weeks 20 and 24, 63 percent of patients treated with Gattex achieved at least a 20 percent reduction in weekly PN/IV volume when compared to baseline, versus 30 percent for placebo (p=0.002).
  • After 24 weeks of treatment, PN volume declined by 32 percent (4.4 L/wk) in Gattex-treated patients, versus 21 percent (2.3 L/wk) in the placebo group (p<0.001).
  • After 24 weeks of treatment, 54 percent of Gattex-treated patients were able to reduce the number of infusion days per week by one or more days, compared to 23 percent of those treated with placebo (p=0.005).

The most common adverse reactions (≥10 percent) across all studies with Gattex are abdominal pain, injection site reactions, nausea, headaches, abdominal distension, upper respiratory tract infection. In addition, vomiting and fluid overload were reported in the Phase 3 SBS studies at rates ≥ 10 percent.

For full prescribing information, please visit www.Gattex.com.

About Gattex® (teduglutide [rDNA origin]) for Injection

Gattex® (teduglutide [rDNA origin]) for injection, for subcutaneous use is a novel, recombinant analog of human glucagon-like peptide 2, a protein involved in the rehabilitation of the intestinal lining. Gattex is indicated for the treatment of adult patients with short bowel syndrome (SBS) who are dependent on parenteral support. Significant reductions in mean PN/IV infusion volume from baseline to end of treatment were seen in the Phase 3 studies of Gattex. In addition, some patients were able to achieve independence from PN/IV support during these trials. The most common side effects of Gattex include stomach area (abdomen) pain or swelling, skin reaction where the injection was given, nausea, headache, cold or flu like symptoms, vomiting, and holding too much fluid in the body (swelling of face, ankles, hands or feet).

Gattex has received orphan drug designation for the treatment of SBS from the European Medicines Agency (EMA) and the FDA.

In 2007, NPS granted Takeda GmbH, the rights to develop and commercialize teduglutide outside the United States, Canada, Mexico and Israel. NPS retains all rights to teduglutide in North America. The European Commission granted European market authorization on August 30, 2012 for the medicinal product teduglutide (trade name in Europe: Revestive®) as a once-daily treatment for adult patients with SBS.

Important Safety Information (ISI)

Gattex has been associated with serious risks including:

Neoplastic growth. There is a risk for acceleration of neoplastic growth. Colonoscopy of the entire colon with removal of polyps must be done before initiating treatment with Gattex and is recommended after 1 year. Subsequent colonoscopies should be done as needed, but no less frequently than every 5 years. In case of intestinal malignancy discontinue Gattex. The clinical decision to continue Gattex in patients with active non-gastrointestinal malignancy should be made based on risk and benefit considerations.

Intestinal obstruction. In patients who develop obstruction, Gattex should be temporarily discontinued pending further clinical evaluation and management.

Biliary and pancreatic disease. Patients should undergo laboratory assessment (bilirubin, alkaline phosphatase, lipase, amylase) before starting Gattex. Subsequent laboratory tests should be done every 6 months. If clinically meaningful changes are seen, further evaluation is recommended including imaging, and continued treatment with Gattex should be reassessed.

Fluid overload. There is a potential for fluid overload while on Gattex. If fluid overload occurs, especially in patients with cardiovascular disease, parenteral support should be appropriately adjusted, and Gattex treatment reassessed.

Prescribers should select the appropriate patients to receive Gattex in accordance with the approved prescribing information, discuss the benefits and risks of Gattex with patients, and monitor patients as specified in the approved prescribing information and report adverse events to NPS' Gattex information line at 1-855-5GATTEX (1-855-542-8839) or event/product complaint line at 1-855-215-5550.

About NPS Pharmaceuticals

NPS Pharmaceuticals is a biopharmaceutical company pioneering and delivering therapies that transform the lives of patients with rare diseases worldwide. The company's lead product, Gattex® 0.05 mg/kg/d (Teduglutide [rDNA origin]) for Injection is FDA-approved for the treatment of adult patients with short bowel syndrome (SBS) who are dependent on parenteral support. NPS is also developing Natpara® (rhPTH[1-84]) for the treatment of adult hypoparathyroidism and expects to submit its Biologic License Application (BLA) to the FDA in mid-2013.

NPS's earlier stage pipeline includes two calcilytic compounds, NPSP790 and NPSP795, with potential application in rare disorders involving increased calcium receptor activity, such as autosomal dominant hypocalcemia with hypercalciuria (ADHH). NPS complements its proprietary programs with a royalty-based portfolio of products and product candidates that includes agreements with Amgen, GlaxoSmithKline, Janssen Pharmaceuticals, Kyowa Hakko Kirin, and Takeda GmbH.

"NPS," "NPS Pharmaceuticals," "Gattex," and "Natpara" are the company's 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. Forward looking statements include, but are not limited to, statements concerning our future commercial performance. Risks associated to the company's business include, but are not limited to, the risks associated with any failure by the company to successfully commercialize Gattex, including the risk that physicians and patients may not see the advantages of Gattex and may therefore be reluctant to utilize the product, the risk that private and public payers may be reluctant to cover or provide reimbursement for Gattex, 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, whether as a result of new information, future events or otherwise.

Contacts:

NPS Pharmaceuticals, Inc.
Susan M. Mesco, 908-450-5516
smesco@npsp.com
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