Clinical Benefits Demonstrated with Low-Dose GATTEX(TM) in Phase 3 Short Bowel Syndrome Study



    
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    BEDMINSTER, N.J., Oct. 11 /CNW/ -- NPS Pharmaceuticals, Inc. (Nasdaq:  
NPSP) today reported top-line results from the company's Phase 3 study of its
investigational drug GATTEX(TM) (teduglutide, recombinant GLP-2) in which 83
patients with short bowel syndrome (SBS) received either a low dose of GATTEX,
(0.05 milligrams/kilogram/day), a higher dose (0.10 mg/kg/day) or placebo. The
clinical efficacy endpoint of the study was a reduction in parenteral
nutrition (PN) of at least 20% comparing baseline to weeks 16 to 24, measured
as a graded response to capture reductions up to 100%. In an intent-to-treat
analysis, forty-six percent (46%) of patients receiving the lower dose of
GATTEX (N=35) responded and achieved a highly statistically significant
reduction in PN compared to placebo (p=0.007), with two patients gaining
independence from and discontinuing PN by week 20 and a third patient
discontinuing PN at the end of treatment. Twenty-five percent (25%) of
patients receiving the higher dose of GATTEX (N=32) responded and showed a
trend in the difference between the treatment group and placebo, but this did
not reach statistical significance (p=0.161). The study's criteria for
conducting the statistical analysis of the primary endpoint required that the
results for the high-dose group show statistical significance before the
results of the low-dose group could be considered. However, given the drug's
orphan designation in SBS and the statistically strong (p=0.007) and
clinically meaningful findings in the low-dose group, the company intends to
meet with the FDA to discuss the path to regulatory approval for GATTEX.
    Dr. Stephen O'Keefe, professor of medicine and director of the Center for
Intestinal Health & Nutrition Support, University of Pittsburgh Medical
Center, said, "Judging from these top-line results, teduglutide is an exciting
new treatment option for our patients with intestinal failure due to massive
intestinal loss. We eagerly await the peer review and publication of the full
results of this international, multi-center clinical trial to determine the
specific indications for this new therapeutic advance."
    In this Phase 3 study, there were no statistical differences in the
incidence rates of adverse events or serious adverse events among the
treatment groups when compared to placebo.
    The study's Data Safety Monitoring Board (DSMB) found that GATTEX was
generally well tolerated and demonstrated clinical benefits. Additionally, the
DSMB supported the company's recommendation to continue the ongoing extension
study.  Ninety-two percent (92%) of the 71 patients who completed the Phase 3
trial enrolled in the extension study.
    Dr. Tony Coles, president and CEO of NPS, stated: "The results of the
study underline the importance of GATTEX as a potential new standard of care
for SBS. We are particularly encouraged to see a reduction in PN over six
months in patients with SBS who received the lower dose of GATTEX. Patients
who responded to this dose were able to reduce their reliance on parenteral
nutrition by over 20%, which represents a clinically meaningful benefit, and
we are very excited that two of the 35 patients on the lower dose were able to
eliminate their PN entirely by week 20, and a third patient was also able to
stop PN altogether at week 24. We look forward to presenting these findings at
an upcoming medical meeting and further exploring the full range of clinical
benefits of GATTEX. We remain committed to making GATTEX available to patients
as soon as possible and intend to meet with regulatory agencies to discuss
next steps for regulatory approval. We also plan to continue our current
exploration of GATTEX in other indications with high unmet needs, including
chemotherapy-induced GI mucositis and necrotizing enterocolitis."
    There are several hypotheses that may explain the higher response in the
low-dose group versus the higher-dose group. One theory is that, at higher
doses, GLP-2 suppresses appetite and it is possible that patients on the
higher dose consumed fewer calories from food and thus did not decrease their
PN regimens. A second hypothesis is that GLP-2 exerts various dose-dependent
effects and may act by increasing nutrient absorption at low-doses while
higher doses of GLP-2 may have a greater effect on mucosal and epithelial
regeneration.
    Dr. Daniel Drucker, director, Banting and Best Diabetes Centre at the
University of Toronto and the scientist who discovered the role of GLP-2,
commented, "Recently published animal studies demonstrate that lower doses of
GLP-2 can enhance nutrient absorption through enhancement of mechanisms
promoting nutrient transport across the gut epithelium and via improved
intestinal cell survival, while higher doses of GLP-2 can result in mucosal
regeneration. These observations suggest that lower doses of GATTEX may have
the greatest potential for effectively treating short bowel syndrome by
improving nutrient absorption, while higher doses of GATTEX may have the
greatest potential for effectively treating other gastrointestinal disorders
where mucosal regeneration may be more important."
    
    Study Design and Top-Line Results
    
    This multicenter, double-blind, international Phase 3 trial was designed
to evaluate the efficacy, safety, tolerability and pharmacokinetics of GATTEX
compared with placebo in patients with parenteral nutrition (PN)-dependent
short bowel syndrome. Eighty three (83) patients who were enrolled in the
trial were randomly assigned to receive daily subcutaneous injections of 0.05
milligrams or 0.10 milligrams of GATTEX per kilogram of body weight or a
placebo for six months after an evaluation period of three days to eight weeks
and a period of stabilization of four to eight weeks. A total of 71 patients
completed the study with a 14.5% dropout rate.
    The clinical efficacy endpoint of the study was a reduction in parenteral
nutrition (PN) of at least 20% comparing baseline to weeks 16 to 24, measured
as a graded response to capture reductions up to 100%.
    The dose levels were selected based on the results of the GATTEX Phase 2
proof-of-concept study where doses of 0.03, 0.10 and 0.15 mg/kg/d were
administered. Since this study had few subjects in the 0.03 mg/kg/d low dose
group, it proved difficult to determine the effects of a low dose. Therefore a
low dose of 0.05 mg/kg/d was selected for the Phase 3 study. The highest dose
(0.15mg/kg/d) did not seem to provide any additional benefit compared to the
0.10 mg/kg/d dose, therefore the 0.10 mg/kg/d dose was selected as the maximum
dose for the Phase 3 study.
    Sixteen of the 35 patients (45.7%) receiving the low dose of GATTEX (0.05
milligrams/kilogram/day) demonstrated a 20 percent or greater reduction in
parenteral nutrition (PN) (p-value 0.007), compared to eight of 32 patients
(25%) in the high-dose group (0.10 mg/kg/day) (p-value 0.161), and one of 16
patients (6%) in the placebo group.
    In this Phase 3 study, there were no statistical differences in the
incidence rate of adverse events or serious adverse events among the treatment
groups when compared to placebo.
    
    Statistical Analysis
    
    The primary endpoint, originally a reduction of 20% or greater in PN
measured at weeks 20 to 24, was expanded to account for duration and magnitude
of effect.  Pair-wise treatment comparisons were made using a rank analysis of
covariance with strata for the baseline PN consumption level used for the
stratification of the randomization and treatment group with the baseline
weekly PN volume as a covariate. A step-down sequential testing procedure was
used to analyze dose response.
    In the first step of the statistical analysis, the high-dose teduglutide
group was compared with the placebo group using a 0.05 significance level. If
the high-dose group was not statistically significantly different from the
placebo group, no further comparisons would be made. If the high-dose group
showed statistical significance, comparisons were to continue to a second
analysis step, where the low dose was to be compared with the placebo.
    
    Phase 2 Proof-of-Concept Study Results
    
    In the Phase 2 GATTEX proof-of-concept study, the drug was given by
subcutaneous injection for 21 days to 16 patients with SBS. Three patients
received 0.03 mg/kg/day, ten patients received 0.10 mg/kg/day, and three
patients received 0.15 mg/kg/day. Results of the Phase 2 study indicated that
GATTEX was safe and well-tolerated, resulted in intestinal epithelial
regeneration and significantly increased intestinal absorption and body weight
in parenteral-nutrition-dependent SBS patients.
    
    About SBS
    
    SBS is a condition resulting from the surgical removal of significant
portions of the bowel following injury or illness. There are 16,000 to 20,000
adult patients with SBS in the United States. Regulatory authorities in the
U.S. and European Union have granted orphan drug status to teduglutide for its
potential use, if approved, in treating SBS. Symptoms of SBS include diarrhea,
dehydration, malnourishment, and weight loss caused by an inadequate
absorption of nutrients and fluids from the diet. Long-term complications of
the condition may include an increased risk of systemic infections due to the
presence of an intravenous feeding line, degenerative changes in the bones and
nerves due to vitamin and mineral deficiencies, and liver failure. Potential
benefits derived from reduced dependence on intravenous feeding may include
improved nutrition, lower rates of infections, and improved quality of life
due to more time away from intravenous feeding, which may provide greater
mobility and improved sleep. More information about SBS is available on the
website, http://www.shortbowel.com and http://www.glucagon.com.
    
    About GATTEX
    
    A potential first-in-class drug, GATTEX is a proprietary analog of
naturally occurring human glucagon-like peptide 2 (GLP-2), a peptide secreted
primarily in the distal intestine and involved in the regeneration and repair
of the intestinal epithelium. A previous Phase 2 proof-of-concept clinical
study in patients with SBS showed that daily subcutaneous injections of GATTEX
resulted in significant regeneration of the intestinal lining and improved
dietary absorption of nutrients and fluids. Once the company has completed its
analysis of data from the Phase 3 SBS study, it expects to pursue a pre-NDA
meeting with the U.S. Food and Drug Administration to discuss its potential
plan for submitting a New Drug Application. NPS is also pursuing development
of GATTEX as a possible treatment for chemotherapy-induced gastrointestinal
mucositis in cancer patients and necrotizing enterocolitis in preterm infants.
    
    Conference Call Information
    
    A conference call will be held today at 9:00 a.m. EDT. To participate in
the call, dial (866) 770-7125 with passcode 66355061. International callers
may dial (617) 213-8066 using the same passcode. In addition, live audio of
the conference call will be simultaneously broadcast over the Internet and may
be accessed on the company's home page, http://www.npsp.com. A conference call
replay will be available until October 22, 2007 at (888) 286-8010, or (617)
801-6888 for international callers, with passcode 47718436. The webcast will
be available for replay and iPod(R) download for the same period.
    Note: 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 management'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. All information in this press release is as of October 11, 2007
and we undertake no duty to update this information. A more complete
description of these risks can be found in our filings with the Securities and
Exchange Commission, including our Annual Report on Form 10-K for the
year-ended December 31, 2006 and our Quarterly Report on Form 10-Q for the
quarter-ended June 30, 2007.




For further information:

For further information: Brandi Simpson of NPS Pharmaceuticals, 
+1-908-450-5616; or Media Contact, Justin Jackson of Burns McClellan, 
+1-212-213-0006, for NPS Pharmaceuticals, Inc. Web Site: http://www.npsp.com  
                http://www.shortbowel.com                 
http://www.glucagon.com

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