Findings Presented at ENDO 2013 Support Therapeutic Potential of Natpara® as
Parathyroid Hormone Replacement Therapy in Patients with Hypoparathyroidism
BEDMINSTER, N.J. -- June 17, 2013
NPS Pharmaceuticals, Inc. (NASDAQ:NPSP), a biopharmaceutical company
pioneering and delivering therapies that transform the lives of patients with
rare diseases worldwide, yesterday presented findings supporting the
therapeutic potential of Natpara® (recombinant full-length human parathyroid
hormone or rhPTH [1-84]) in poster sessions at ENDO 2013, The Endocrine
Society’s 95th Annual Meeting in San Francisco, CA. Natpara is a bioengineered
replica of human parathyroid hormone that is being developed by NPS for adults
with hypoparathyroidism, a rare and complex endocrine disorder that is
characterized by insufficient levels of parathyroid hormone, the body’s
principal regulator of calcium and phosphorus.
“These findings suggest Natpara may provide an important new treatment option
for patients with hypoparathyroidism by improving the calcium and phosphorus
mineral imbalance associated with this complex disorder while significantly
reducing the dependence on calcium and vitamin D supplementation,” said Roger
Garceau, MD, executive vice president and chief medical officer of NPS
Pharmaceuticals. “Our growing collection of clinical data for Natpara supports
its therapeutic potential as the first replacement therapy targeting the
underlying cause of adult hypoparathyroidism and we look forward to filing our
U.S. Biologic License Application later this year.”
Hypoparathyroidism is the only classic endocrine disorder without an
FDA-approved replacement therapy. Current treatment approaches focus on
symptom management through high doses of calcium and active vitamin D, which
can lead to serious side effects and long-term consequences.
Treatment with Natpara resulted in maintained serum active vitamin D levels
despite a significant reduction in active vitamin D requirements.
In a poster presentation on Sunday, June 16, lead study investigator Dolores
M. Shoback, M.D., Professor in Residence at the University of California, San
Francisco School of Medicine, presented results analyzing the effects of
Natpara on vitamin D metabolism in patients with hypoparathyroidism in two
clinical trials, a Phase 1 study and REPLACE, a Phase 3 registration study.
The results indicate that Natpara treatment maintains serum levels of active
vitamin D in the normal range despite a significant reduction in active
vitamin D requirements, while maintaining serum calcium at or near baseline,
and reducing 24-hour urinary calcium in patients deficient in endogenous PTH
All patients enrolled were prescribed calcium and active vitamin D supplements
(calcitriol or 1 alpha calcifediol). In the Phase 1 study, patients received
two doses of Natpara (50 and 100 μg), separated by a washout period of seven
days or more.
In the Phase 1 study, serum active vitamin D increased to maximum
baseline-adjusted level of 27.2 ±18.3 and 19.6 ±11.0 pg/ml with the 50-µg and
100µg doses of Natpara, respectively. 24-hour urine calcium excretion
decreased by 13% and 23% with the 50- and 100µg doses, respectively. Serum
calcium levels showed maximum mean increases of 0.7 to 0.9 mg/dL 12 hours
after the Natpara injection and remained above baseline levels after 24 hours
with either dose.
In REPLACE, 43% (36/84) patients treated with Natpara became independent of
active vitamin D and reduced daily calcium to less than 500 mg/day versus 5%
(2/37) patients in the placebo group by week 24 (P<0.001). Active vitamin D
doses were decreased by 79% in the Natpara group (n=90) and 30% in the placebo
group (n=44) at week 24 (P<0.001). Despite reductions in active vitamin D use
by Natpara-treated patients, active vitamin D levels did not change. In
contrast, vitamin D showed a greater mean decrease at week 24 in the Natpara
group versus the placebo group.
At week 24, mean urine calcium decreased by -74 ±190 mg/24 hours in the
Natpara group and -84 ±169 mg/24 hours in the placebo group (P=0.06). In the
placebo arm, reductions in urine calcium were mirrored by decreased total
serum calcium levels. In contrast, total serum calcium remained above or near
the baseline levels in Natpara-treated patients. Serum calcium levels were
significantly higher in the Natpara group versus the placebo group at weeks
1-16 (P<0.05) but not at week 24.
Natpara may provide better control of phosphate homeostasis in addition to the
improved control of serum and urinary calcium
In a poster presentation on Sunday, June 16, lead study investigator Bart L.
Clarke, M.D., Associate Professor of Medicine at the Mayo Clinic in Rochester,
MN, presented results analyzing the effects of Natpara on serum phosphate
levels in patients with hypoparathyroidism in two clinical trials, a Phase 1
study and REPLACE, a Phase 3 registration study.
In the Phase 1 study, patients received two doses of Natpara (50 or 100 μg per
day), separated by >=7 day washout. In the REPLACE study, serum and urine
samples were collected at various pre-defined timepoints throughout the study
Both studies demonstrated substantial effects of Natpara on serum and urinary
phosphate levels. In the Phase 1 study, doses of Natpara (50-µg, n=6; 100-µg,
n=7) decreased mean serum phosphate levels significantly by a maximum of 1.5
mg/dL within five hours. Natpara also increased total 24-hour urinary
phosphate excretion by 51% (50-µg) and 60% (100-µg). In REPLACE, a marked
decrease in serum phosphate in the Natpara group followed initiation of study
drug and was maintained throughout the treatment period, with serum phosphate
declining from baseline of 4.53 ±0.7 to 4.08 ±0.7mg/dL at Week 24; serum
phosphate did not change from baseline in the placebo group. The Natpara group
showed a significantly greater decrease over placebo in serum phosphate values
at all time points (P≤0.003); at Week 24, the mean change from baseline (least
square±SE) was −0.47 ±0.07 mg/dL for Natpara versus −0.06 ±0.10 mg/dL for
placebo (P<0.001). In both groups, 24-hour urine phosphate excretion was
reduced from baseline at Week 24; these results were not statistically
About the REPLACE Study
REPLACE was a randomized, double-blind, dose-escalating, placebo-controlled
Phase 3 registration study that investigated the use of Natpara for the
treatment of adults with hypoparathyroidism at more than 30 sites in North
America and Europe.
The study consisted of an average 10-week screening and stabilization period
followed by a 24-week treatment period marked by randomization (2:1) to 50µg
once daily Natpara or placebo. Following randomization, subjects underwent
staged reductions in calcium and vitamin D supplementation, while maintaining
stabilized serum calcium. If needed, step-wise up-titration of study drug
(Natpara or placebo) to a dose of 75 µg and then if necessary to 100 µg over a
six to eight week period was performed. Subjects continued on their final dose
through Week 24. A follow-up period without study drug lasted from Week 24 to
In an intent-to-treat analysis, 53 percent (48/90) of Natpara-treated patients
achieved the primary endpoint versus 2 percent (1/44) of placebo-treated
patients (P<0.001). The primary efficacy endpoint of REPLACE was to
demonstrate by Week 24 at least a 50 percent reduction from baseline of both
oral calcium supplementation and active vitamin D metabolite/analog therapy
and a total serum calcium concentration that was normalized or maintained
compared to baseline (≥7.5 mg/dL).
At Week 24, 43 percent (36/84) of patients treated with Natpara were able to
achieve independence from active vitamin D therapy and required only a calcium
supplementation dose of 500 mg/day or less, as compared to five percent (2/37)
of patients treated with placebo (P<0.0001).
Despite the large reductions in supplementation, serum calcium remained at or
above baseline levels for the Natpara-treated patients. In this study, Natpara
was generally well-tolerated. Overall rates of adverse events during the
24-week treatment period were similar (90% vs. 96% Natpara and placebo,
respectively). The spectrum of adverse events reflected underlying disease
pathophysiology with most common being paresthesias, muscle spasms, headache,
and hypocalcemia. Based on these study findings, Natpara may show promise as
an effective replacement therapy for hypoparathyroidism.
Hypoparathyroidism is a rare endocrine disorder in which the body produces
insufficient levels of parathyroid hormone, the principal regulator of calcium
and phosphorus. When the body has too little parathyroid hormone, blood
calcium levels drop and phosphorus levels increase, which can cause a number
of physical and mental symptoms, including uncontrollable muscle spasms and
cramps, tetany, seizures, fatigue, anxiety, and depression. There is currently
no FDA-approved replacement therapy for hypoparathyroidism, which is currently
managed with large doses of calcium supplementation and active vitamin D
therapy to raise the calcium levels in the blood and reduce the severity of
symptoms. Over time, calcium may build up in the body and result in serious
health risks, including calcifications in the kidneys, heart or brain.
Hypoparathyroidism is believed to affect as many as 100,000 Americans.
About NPS Pharmaceuticals
NPS Pharmaceuticals is a global biopharmaceutical company pioneering and
delivering therapies that transform the lives of patients with rare diseases
worldwide. The company’s lead product, Gattex® (teduglutide [rDNA origin]) for
injection is approved in the U.S. for adult Short Bowel Syndrome (SBS)
patients who are dependent on parenteral support. Teduglutide is also approved
for adult SBS in the European Union under the brand name Revestive®. NPS is
also developing Natpara® (recombinant full-length human parathyroid hormone or
rhPTH [1-84]) for the treatment of adult hypoparathyroidism and, subject to
the resolution of certain manufacturing issues, expects to submit its Biologic
License Application (BLA) to the FDA in 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 and Kyowa
Hakko Kirin. Additional information about NPS is available through its
corporate website, http://www.npsp.com.
“NPS,” “NPS Pharmaceuticals,” “Gattex,” “Natpara”, “Preotact”, and “Revestive”
are the company's trademarks.
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 the
company’s future financial 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 (teduglutide [rDNA
origin])for injection, 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, the risk that the company may be unable to
resolve the manufacturing issue in order to submit its BLA for Natpara, the
risks associated with the company's strategy, global macroeconomic conditions,
the impact of changes in management or staff levels, the effect of legislation
effecting healthcare reform in the United States, 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.
NPS Pharmaceuticals, Inc.
Susan M. Mesco, 908-450-5516
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