Palopegteriparatide

Ascendis Pharma developed palopegteriparatide using a TransCon carrier-and-linker design. PTH(1–34) is attached to an inert carrier and released gradually after injection. The aim is continuous hormone replacement for glands that cannot produce enough PTH. Yorvipath received US approval in 2024.

The injected prodrug releases active PTH(1–34) over about 24 hours, rather than producing the rapid peak and decline of standard teriparatide. Released hormone activates PTH-1 receptors and restores calcium regulation through the kidney, vitamin-D activation and bone.

In hypoparathyroidism, steady replacement aims to maintain normal blood calcium while reducing high-dose calcium and active-vitamin-D requirements. At 26 weeks in the Phase 3 PaTHway trial, most treated patients met the composite endpoint of normal calcium plus independence from conventional therapy; a large majority became independent of calcium and active vitamin D.

FDA approved Yorvipath for adult hypoparathyroidism in 2024, after European approval. It is given under the skin once a day. Labeling warns of a potential osteosarcoma risk based on rat studies of PTH analogs and advises against use in people at increased risk of that cancer.

Adult hypoparathyroidism is the treatment setting. Replacement seeks to maintain calcium while reducing reliance on conventional calcium and active-vitamin-D supplementation. Its steady-exposure design distinguishes it within PTH replacement therapy.

Common adverse effects include injection reactions, flushing, lightheadedness or orthostatic blood-pressure reduction, headache, back pain, diarrhea, hypercalcemia and sore throat. Calcium can become too high or too low, particularly during adjustment. Serious considerations include hypersensitivity and the potential osteosarcoma risk identified from PTH-analog rat studies.