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
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
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
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.
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.