NPS Pharmaceuticals, Inc., a biopharmaceutical company pioneering and delivering therapies that transform the lives of patients with rare diseases worldwide, has submitted its Biologic License Application (BLA) to the US Food and Drug Administration (FDA) for Natpara (recombinant human parathyroid hormone 1-84, rhPTH(1-84)).

Natpara is a bioengineered replacement for endogenous parathyroid hormone (PTH) that NPS has developed for the treatment of hypoparathyroidism, a rare endocrine disorder in which the body produces insufficient levels of parathyroid hormone, a principal regulatory of the body’s mineral homeostasis.

“Submitting our BLA for Natpara is a significant step forward for NPS in our effort to bring the first replacement therapy to patients with hypoparathyroidism,” said Francois Nader, MD, president and chief executive officer of NPS Pharmaceuticals. “Hypoparathyroidism patients face a significant burden of disease given the multitude of physical, cognitive, and emotional symptoms associated with this disorder.”

PTH plays a central role in a variety of critical physiological functions, including closely modulating serum calcium and phosphate, regulating renal excretion of calcium and phosphate, activating vitamin D, and maintaining normal bone turnover. In patients with hypoparathyroidism, insufficient levels of PTH lead to low serum calcium, high serum phosphate, increased urinary calcium excretion, and decreased urinary phosphorus excretion. PTH deficiency can also disrupt skeletal homeostasis, leading to bone abnormalities. In addition, patients with insufficient levels of PTH are unable to convert native vitamin D into its active state to properly absorb dietary calcium.

Acute symptoms of hypoparathyroidism are largely due to hypocalcemia and include fatigue, muscle spasms and cramps, tingling, tetany, seizures, brain fog/mental lethargy, anxiety, and depression. In the absence of an approved parathyroid replacement therapy, the standard approach focuses on using high doses of calcium and active vitamin D to increase calcium levels in the blood and reduce the severity of hypocalcemic symptoms. However, balancing the administration of supplements is challenging due to calcium fluctuations and the long-term use of high doses of calcium and vitamin D may lead to serious complications, including long-term renal damage. In addition, because serum phosphate levels are elevated when PTH is missing, increasing serum calcium may lead to irreversible calcium-phosphate deposits in the kidneys, arteries or brain. Further, supplements do not correct the abnormal bone metabolism due to PTH deficiency or enable the activation of vitamin D.

Natpara is a bioengineered replica of human parathyroid hormone designed to replace the missing hormone, which is a practice used successfully in treating other classic endocrine disorders. The company’s clinical development program for Natpara includes 12 pharmacology studies, five efficacy and safety studies in hypoparathyroidism, and a supporting development programme consisting of seven studies in osteoporosis. The pivotal phase III study known as REPLACE, was a randomized, double-blind, placebo controlled study of 134 patients with hypoparathyroidism.

The results from the REPLACE study were recently published in The Lancet Diabetes & Endocrinology.

Hypoparathyroidism is a rare endocrine disorder in which the body produces insufficient levels of parathyroid hormone, a principal regulator of the body’s mineral homeostasis. The FDA has granted orphan drug status for Natpara for the treatment of hypoparathyroidism.