Palopegteriparatide (Yorvipath): What It Is and How It Works

At a glance

What is palopegteriparatide?

Palopegteriparatide, sold under the brand Yorvipath, is a long-acting form of parathyroid hormone built using a sustained-release (TransCon) design: the active PTH(1-34) is attached to an inert carrier through a linker that slowly releases the hormone over the day. The goal is to supply parathyroid hormone continuously, the way healthy glands do, in people whose own glands cannot. Palopegteriparatide, developed by Ascendis Pharma, was approved in the United States in 2024.

How does palopegteriparatide work?

Palopegteriparatide is an inactive prodrug that gradually releases active PTH(1-34) after injection, producing steady hormone levels across 24 hours rather than the sharp peak and rapid fall of standard teriparatide. The released hormone binds the PTH-1 receptor and restores calcium balance through the kidney, vitamin D activation, and bone, replacing the hormone that is deficient in hypoparathyroidism. The continuous exposure is the point: in hypoparathyroidism, steady parathyroid hormone keeps blood calcium normal while reducing reliance on high-dose calcium and active vitamin D. In the phase 3 PaTHway trial, most patients on the drug met a composite goal of normal calcium with independence from conventional therapy at 26 weeks, and the large majority became independent of calcium and active vitamin D.

Is it FDA-approved?

Yes. Palopegteriparatide was approved by the FDA in 2024 as Yorvipath for hypoparathyroidism in adults, following earlier approval in Europe. Its label warns of a potential risk of osteosarcoma, based on rat studies of parathyroid hormone analogs, and it is not recommended for people at increased risk of that cancer. It is given as a once-daily subcutaneous injection.

What is palopegteriparatide prescribed for?

Palopegteriparatide is prescribed for the treatment of hypoparathyroidism in adults, to maintain blood calcium and reduce the need for calcium and active vitamin D supplementation. It offers a steady-exposure alternative within the parathyroid hormone replacement class.

What are the side effects?

According to the prescribing information, common side effects include:

• Injection-site reactions
• Flushing, lightheadedness, or a drop in blood pressure on standing
• Headache
• Back pain
• Diarrhea
• High blood calcium
• Sore throat More serious considerations include:
• A potential risk of osteosarcoma, based on rat studies of parathyroid hormone analogs
• High or low blood calcium, particularly when doses are adjusted
• Hypersensitivity reactions

Evidence strength

FDA approved: Palopegteriparatide is FDA-approved for hypoparathyroidism, supported by the phase 3 PaTHway trial showing normal calcium and independence from conventional therapy.

Sources: FDA prescribing information for Yorvipath; the PaTHway trial (Khan et al., Journal of Bone and Mineral Research, 2023, DOI: 10.1002/jbmr.4726), indexed on PubMed. This document is educational and does not constitute medical advice.