NPS Pharmaceuticals, Inc. (NASDAQ: NPSP), a specialty pharmaceutical company developing orphan therapeutics for rare gastrointestinal and endocrine disorders, today announced positive top-line results from REPLACE, a Phase 3 registration study of NPSP558, the company's bioengineered replica of human parathyroid hormone (rhPTH 1-84), in adult hypoparathyroidism patients. NPS has received orphan drug status for NPSP558 for the treatment of hypoparathyroidism, a rare endocrine disorder in which the body produces insufficient levels of parathyroid hormone, the principal regulator of calcium and phosphorus, and for which there is no FDA-approved replacement therapy. The symptoms of hypoparathyroidism are typically managed with large doses of oral calcium supplementation and active vitamin D therapy to reduce the severity of symptoms. The prolonged use of oral calcium supplementation and active vitamin D therapy may result in serious long-term health complications.
In an intent-to-treat analysis, 53 percent (48/90) of NPSP558-treated patients achieved the primary endpoint versus 2 percent (1/44) of placebo-treated patients (p<0.0001). The primary efficacy endpoint was defined as a 50 percent or greater reduction in oral calcium supplementation and active vitamin D therapy and a total serum calcium concentration that was normalized or maintained compared to baseline after 24 weeks of treatment. REPLACE was a 28-week, double-blind, placebo-controlled study. At week 24, 43 percent (36/84) of patients treated with NPSP558 were able to achieve independence from active vitamin D therapy and a calcium supplementation dose of 500 mg/day or less, as compared to five percent (2/37) for patients treated with placebo (p<0.0001).
"Considering hypoparathyroidism is the only endocrine disorder for which we do not have an approved replacement hormone to treat the underlying condition, these data indicate that NPSP558 may offer a valuable option to achieve a physiological treatment and outcome by delivering the missing hormone," said Bart Clarke, MD, associate professor of medicine at the Mayo Clinic and an investigator for the REPLACE study. "Doctors currently can only provide supportive care aimed at managing the symptoms and patients are faced with striking a balance between managing their symptoms and avoiding the long-term risks associated with current treatments, which can result in kidney stones, kidney damage, and even kidney failure."
The REPLACE study showed that NPSP558 was well-tolerated. Thirteen of the 134 randomized subjects discontinued the study early, of which seven were placebo-treated and six were NPSP558-treated. Overall, the incidence of adverse events and serious adverse event were similar among both groups.
"These positive results from our Phase 3 REPLACE study are an important milestone and bring us one step closer to our goal of providing hypoparathyroidism patients with a much-needed replacement therapy," said Francois Nader, MD, president and chief executive officer of NPS Pharmaceuticals. "Based on these results we expect to file for FDA approval of NPSP558 in 2012. We thank the patients, clinical investigators, and study coordinators for their participation in this pivotal study."