Until recently, hypoparathyroidism remained among the few hormonal insufficiency states not treated by the replacement of the missing hormone. Conventional therapy with vitamin D analogs and calcium supplementation does not control symptoms in approximately one third of patients, and may lead to renal insufficiency or failure due to progressive nephrocalcinosis, as well as soft tissue calcifications. Currently available therapies are limited in their ability to address the underlying disease pathophysiology.
TransCon parathyroid hormone (PTH) is designed to address the major limitations of current therapies by simultaneously normalizing blood and urinary calcium levels as well as bone turnover. If approved, once-daily administration is expected to provide hypoparathyroidism patients with tight calcemic control without hyper- or hypocalcemia.
Leveraging our TransCon technology, TransCon PTH is a PTH prodrug that releases free PTH in the physiological range. It is designed to closely approximate free PTH levels observed following continuous infusion of teriparatide, which has been shown to be superior to daily injections.
Recent preclinical work supports the target product profile. Pharmacokinetic studies demonstrate an infusion-like profile following daily administration, with administration of a single dose of TransCon PTH leading to a sustained elevation of serum calcium lasting more than 24 hours. In preclinical models of hypoparathyroidism, daily administration of TransCon PTH provided better calcemic and phosphatemic control compared to daily injections of PTH(1-84), the active ingredient in a currently available therapy.
Building on these positive results, Ascendis Pharma currently plans to submit an Investigational New Drug Application for TransCon PTH in the second quarter of 2017.
Hypoparathyroidism is defined as a decrease or lack of parathyroid hormone, leading to low levels of calcium in the blood and bones and an increase in serum phosphorus. Calcium and/or vitamin D supplementation can help relieve symptoms, but these treatments can have undesirable side effects including an increased risk of kidney stones and chronic kidney disease.