Recombinant Human Parathyroid Hormone (1–84): A Review in Hypoparathyroidism

Abstract

Full-length recombinant human parathyroid hormone [rhPTH (1-84); Natpara(®)] is approved in the USA as an adjunct to calcium and vitamin D therapy for control of hypocalcaemia in patients with hypoparathyroidism. This article reviews the clinical efficacy and tolerability of rhPTH (1-84) in hypoparathyroidism and summarizes its pharmacological properties. In a pivotal phase III trial, subcutaneous rhPTH (1-84) was effective in maintaining albumin-corrected total serum calcium levels while reducing/eliminating the need for oral calcium and active vitamin D. rhPTH (1-84) had a generally acceptable tolerability profile in this trial, with <3% of patients discontinuing treatment because of adverse events. Commonly occurring adverse reactions included hypocalcaemia, hypercalcaemia and hypercalciuria. As the first PTH replacement therapy for hypoparathyroid patients with hypocalcaemia, rhPTH (1-84) is an effective regimen, has generally acceptable tolerability and represents an important advance for the management of hypoparathyroidism.

Identification of an orally active small-molecule PTHR1 agonist for the treatment of hypoparathyroidism

“…An important benefit of PTH replacement therapy when treating hypoparathyroidism is that it can reduce the doses of Ca and vitamin D 3 while maintaining serum Ca levels, and this has been clinically demonstrated by combining hPTH(1–84) with conventional vitamin D and Ca therapy12. We therefore examined the effect of PCO371 in combination with alfacalcidol (1α-hydroxycholecalciferol) in TPTX rats.…”

“…14). Recently, PTH replacement therapy with recombinant hPTH(1–84) has been approved to treat hypoparathyroidism; however, as a peptide it requires daily subcutaneous injections1229. Once-daily dosing of hPTH(1–84) can increase Ca to peak levels at around 7 h after administration, and the effects are observed for up to 24 h. However, hypercalcemia was observed at peak times in 71% of hPTH(1–84)-treated patients, and this suggests that a lower dose or more frequent daily dosing regimens may be more beneficial for some patients30.…”

“…Chronic hypercalciuria can cause irreversible renal damage and eventual renal failure81011. To avoid such risk, studies have focused on PTH replacement therapy using the full-length, native PTH molecule called human PTH(1–84) (hPTH(1–84))1213 or a synthetic fragment called human PTH(1–34) (hPTH(1–34))81415. PTH replacement therapy has been demonstrated to ameliorate the blood, renal, skeletal and neuropsychological features of hypoparathyroidism to a greater extent than conventional treatment.…”

“…PTH replacement therapy has been demonstrated to ameliorate the blood, renal, skeletal and neuropsychological features of hypoparathyroidism to a greater extent than conventional treatment. hPTH(1–84) and hPTH(1–34) can elevate serum Ca without raising urinary Ca in patients with hypoparathyroidism; however, due to the short half-lives of these compounds, frequent injections or continuous pump delivery is necessary to maintain serum Ca levels at a steady level121315. The peptidic nature (or poor oral bioavailability) of PTH(1–34) has limited its use in the treatment of osteoporosis, since daily subcutaneous injection of hPTH(1–34) is also used clinically for treating severe osteoporosis116.…”

Leczenie ciężkiej, zagrażającej życiu hipokalcemii ludzkim rekombinowanym teryparatydem pacjentów z pooperacyjną niedoczynnością przytarczyc — seria przypadków

“…PTH deficiency -was the only hormone deficiency disease without approved substitution therapy. Since 2015, full-length recombinant human parathormone [rhPTH ; Natpara] has been approved in the USA as an adjunct to calcium and vitamin D to control hypocalcaemia in patients with hypoparathyroidism [53]. The onset and duration of treatment has not been specified and the most dangerous potential complication observed in rat studies is osteosarcoma of bones [54].…”