Hypoparathyroidism (HP) is classified into congenital HP and acquired HP, with the majority cases caused by surgery following damage or accidental removal of the parathyroid glands. Clinical manifestations include weakness, severe muscle spasms, paresthesias, brain fog, impaired judgment and headache. The long-term complications include increase risk of calcifications occurring within the brain (basal ganglia), nephrocalcinosis and kidney stones, which can increase risk of seizures and impaired renal function etc.
Standard of care (SoC) with active vitamin D and calcium supplementation cannot resolve major clinical issues1. It is difficult to resolve hypocalcemia issue in some HP patients. In addition, SoC is associated with long-term complications such as hypercalciuria, kidney stones, nephrocalcinosis and calcifications in the brain2. SoC also does not address the issue of reduced bone turnover caused by lacking PTH. PTH replacement will normalize blood and urinary calcium levels and then will not induce hypercalciuria, kidney stone and nephrocalciunosis.
TransCon PTH is an investigational long-acting prodrug of PTH in development as a potential ideal replacement therapy for HP. By providing PTH (1-34) at physiologic levels for 24 hours a day, TransCon PTH demonstrated in phase 1 a flat infusion like profile with low PTH peak as normal human endogenous PTH secretion curve3,4(as illustrated in bellowing figure). We expect TransCon PTH to normalize blood and urinary calcium levels, serum phosphate levels and bone turnover3,4.
TransCon PTH received Orphan Drug Designation (ODD) for the treatment of HP from American FDA. Results of an ongoing phase 2 trial are expected in 2020, followed by submission of regulatory filings to initiate an international multicenter phase 3 trial by end the year.
VISEN Pharma is collaborating with Ascendis and developing relevant clinical studies in China.
《Chinese journal of osteoporosis and bone mineral salt diseases》2018;11(4):323-337.
Mannstadt, M. et al. Hypoparathyroidism. Nat Rev Dis Primers 3, 17055 (2017)