Health & Fitness
Health and Fitness
Health and Fitness
Tue, December 23, 2008
Mon, December 22, 2008
NPS Pharmaceuticals Initiates Phase 3 'REPLACE' Study of NPSP558 in Hypoparathyroidism
BEDMINSTER, N.J.--([ BUSINESS WIRE ])--NPS Pharmaceuticals (NASDAQ: NPSP), a specialty pharmaceutical company focused on developing therapeutics for rare gastrointestinal and endocrine disorders, today announced it has begun patient enrollment in a Phase 3 registration study, known as REPLACE, evaluating NPSP558 for the treatment of adults with hypoparathyroidism. NPSP558 is the company's proprietary recombinant full-length human parathyroid hormone (PTH 1-84), which mimics the action of natural parathyroid hormone. Hypoparathyroidism is a rare condition in which the body produces insufficient levels of parathyroid hormone causing lower than normal levels of calcium in the blood, known as hypocalcemia. There is currently no approved replacement therapy for hypoparathyroidism. NPS believes positive results from REPLACE will enable it to seek U.S. marketing approval for NPSP558 for the treatment of hypoparathyroidism.
"Achieving this important milestone brings us one step closer to filing a marketing application for NPSP558 as the first therapeutic option for hypoparathyroidism, one of the few remaining hormone deficiencies without an approved replacement therapy," said Francois Nader, MD, president and chief executive officer of NPS Pharmaceuticals. "We are encouraged by NPSP558's activity to date and believe it has the optimal mechanism of action to address the significant needs of this underserved patient population. We expect to complete the study and report top line results in the second half of 2010."
REPLACE Study Design
REPLACE is a double-blind, placebo-controlled trial that will randomize approximately 110 patients at over a dozen sites in the United States, Canada and Europe. The primary objective is to demonstrate, over a 24-week treatment period, that once-daily subcutaneous dosing with NPSP558 at doses of 50µg, 75µg or 100µg is a safe and effective hormone replacement therapy for the treatment of patients with hypoparathyroidism.
The study will consist of a maximum 10-week screening and stabilization period followed by a 24-week treatment period marked by randomization (2:1) to NPSP558 50µg (with the potential for titration up to 75µg and 100µg) or placebo. Following randomization, patients will undergo staged reductions in calcium and vitamin D supplementation, while maintaining a serum total calcium within clinically stable limits. If needed, up-titration of study drug to 75 µg or 100 µg in patients over a six to eight week period will be performed. Patients will continue on their final NPSP558 dose through week 24 and a follow-up period will last from week 24 to week 28.
Efficacy will be demonstrated by achievement or maintenance of a normal or clinically acceptable stable albumin-corrected serum total calcium in parallel with reduced requirements for oral supplementation with calcium and treatment with active vitamin D metabolites or analogs.
The responder status is defined as a patient that demonstrates at least a 50 percent reduction from baseline amounts of oral calcium supplementation and at least a 50 percent reduction from baseline amounts of vitamin D metabolite/analog therapy by week 24 of the study. Patients should have a clinically stable serum calcium level that is established to the satisfaction of the investigator at baseline and is maintained or normalized by week 24 of the study.
The secondary objectives of the study include studying the urinary calcium excretion or hypercalciuria, the proportion of patients with maintenance of a calcium phosphate product in the normal range, and the proportion of patients that achieve independence from supplemental active vitamin D metabolite/analog usage or a calcium supplementation dose of 500 mg/day by Week 24
About NPSP558 (parathyroid hormone 1-84 [rDNA origin] injection)
NPSP558 is a recombinant full-length human parathyroid hormone (PTH 1-84), the main hormone that is needed to maintain the balance of calcium in the body. Because it mimics the action of natural parathyroid hormone, NPSP558 has the potential to treat hypoparathyroidism and return the body to a physiological or "eucalcemic" state. In September 2008 at the Annual Meeting of the American Society for Bone and Mineral Research (ASBMR), positive interim data were presented from an investigator-initiated Phase 2 proof-of-concept study of NPSP558 for the treatment of hypoparathyroidism, conducted at Columbia University's College of Physicians and Surgeons with John P. Bilezikian, MD, serving as the principal investigator. The interim data demonstrated that treatment with PTH 1-84 had a beneficial effect on abnormal bone skeletal properties in patients with hypoparathyroidism.
In 2007, the FDA granted orphan drug status for NPSP558 for the treatment of hypoparathyroidism. NPS's partner Nycomed markets PTH 1-84 ex-US as Preotact® for the treatment of osteoporosis in post-menopausal women at high risk of fractures.
About Hypoparathyroidism
NPS has estimated that approximately 65,000 patients suffer from hypoparathyroidism in the U.S. It is one of the few remaining hormone deficiency states without an approved replacement therapy. Because the primary role of parathyroid hormone is to maintain normal calcium levels in blood, themajor consequence of its absence is low circulating calcium levels (hypocalcemia), which can cause tingling of the hands, fingers, and mouth, serious muscle cramping or, in extreme situations, to tetany or convulsions. The goal of currently available treatments for hypoparathyroidism, which include life-long high-dose oral supplementation with calcium and active vitamin D metabolites or analogs, is to reduce the severity of symptoms. However, hypoparathyroidism and the use of oral calcium and vitamin D analogs/metabolites for symptom control can contribute to organ damage and calcification, which is particularly evident in the kidneys.
About NPS Pharmaceuticals
NPS Pharmaceuticals is developing therapeutics for rare gastrointestinal and endocrine disorders with high-unmet medical needs. The company is currently advancing two late-stage programs. Teduglutide, a proprietary analog of glucagon-like peptide-2, is in Phase 3 clinical development for intestinal failure associated with short bowel syndrome as GATTEX™ and in preclinical development for additional intestinal failure related conditions. NPSP558 (parathyroid hormone 1-84 [rDNA origin] injection) is in Phase 3 clinical development as a hormone therapy for hypoparathyroidism. NPS complements its proprietary programs with a royalty-based portfolio of products and product candidates that includes strategic agreements with Amgen, GlaxoSmithKline, Kyowa Kirin, Ortho-McNeil, and Nycomed. Additional information is available at [ http://www.npsp.com ].
"NPS" and "NPS Pharmaceuticals" are the company's registered trademarks. Preotact® is the company's registered trademark in the U.S. 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. Risks associated to NPS's business include, but are not limited to, the risk of not successfully executing its preclinical and clinical studies and not gaining marketing approvals for GATTEX and NPSP558, the risks associated with the implementation of a new business strategy, the risks associated with the company's auction-rate securities, as well as other factors expressed in NPS's periodic filings with the U.S. Securities and Exchange Commission, including its Annual Report on Form 10-K/A 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.
