Findings Presented at ENDO 2013 Support Therapeutic Potential of Natpara® as Parathyroid Hormone Replacement Therapy in Patients with Hypoparathyroidism Business Wire 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 secretion. 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 for analyses. 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 significant (P=0.07). 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 Week 28. 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. About 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. Disclosure notice 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. Contact: NPS Pharmaceuticals, Inc. Susan M. Mesco, 908-450-5516 email@example.com
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Findings Presented at ENDO 2013 Support Therapeutic Potential of Natpara® as Parathyroid Hormone Replacement Therapy in
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