NPS Pharmaceuticals has reported positive top-line results from REPLACE, a phase III 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% (48/90) of NPSP558-treated patients achieved the primary endpoint versus 2% (1/44) of placebo-treated patients. The primary efficacy endpoint was defined as a 50% 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% (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 5% (2/37) for patients treated with placebo.
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.