Palopegteriparatide

Summary

Palopegteriparatide (brand name Yorvipath) is a long-acting, PEGylated prodrug of teriparatide approved for the treatment of chronic hypoparathyroidism in adults. It provides a sustained delivery of PTH(1-34) to mimic physiological parathyroid hormone activity, reducing dependence on calcium and active vitamin D supplementation.

Mechanism of Action

Palopegteriparatide is a PEGylated prodrug of teriparatide (PTH 1-34) that acts as a full agonist at the parathyroid hormone type 1 receptor (PTH1R). Upon subcutaneous administration, the PEG moiety is cleaved to release active teriparatide, activating PTH1R on osteoblasts and renal tubular cells, stimulating bone formation and regulating calcium and phosphate homeostasis. Designed to provide sustained, near-physiologic PTH exposure for hypoparathyroidism.

Routes of Administration

Goals & Uses

• Normalization of serum calcium levelsEndocrine/MetabolicHigh
• Improvement of quality of life in hypoparathyroidismPatient Reported OutcomesModerate
• Reduction of calcium and vitamin D supplementation burdenEndocrine/MetabolicHigh
• Reduction of hypercalciuria and renal complicationsRenalModerate
• Treatment of chronic hypoparathyroidismEndocrine/MetabolicHigh

Contraindications

• Osteosarcoma risk conditions (Paget's disease, prior radiation therapy to skeleton)OncologicHigh
• Hypersensitivity to teriparatide or PEG componentsAllergy/ImmunologicHigh
• HypercalcemiaMetabolic DisorderHigh
• Pediatric patients with open epiphysesPediatricHigh
• Metabolic bone diseases other than hypoparathyroidismMusculoskeletalModerate

Adverse Effects

• HypercalcemiaMetabolicCommon
• Injection site reactionsLocalCommon
• HeadacheNeurologicCommonPain in the head or upper neck
• HypercalciuriaMetabolicUncommon
• NauseaGastrointestinalCommonFeeling of sickness or urge to vomit
• HypocalcemiaMetabolicCommon

Drug Interactions

• BisphosphonatesLow
• Active vitamin D analogs (calcitriol, alfacalcidol)Moderate
• Calcium supplementsModerate
• Thiazide diureticsModerate

Population Constraints

• PregnancyReproductive SafetyRelative
• History of nephrolithiasis or nephrocalcinosisRenalRelative
• Severe renal impairmentOrgan ImpairmentRelative
• Pediatric patientsAgeAbsolute
• BreastfeedingReproductiveRelative

Regulatory Status

• European UnionApprovedApproved: Chronic hypoparathyroidism in adultsEMA approved in 2023 under the brand name Yorvipath. Designated as an orphan medicinal product.
• United StatesApprovedApproved: Chronic hypoparathyroidism in adultsFDA approved in 2024 under the brand name Yorvipath. Received Orphan Drug Designation.
• United KingdomApprovedApproved: Chronic hypoparathyroidism in adultsApproved by MHRA following EMA authorization; available as Yorvipath.

Approved by the EMA in 2023 for adults with chronic hypoparathyroidism. FDA approved in 2024 under the brand name Yorvipath for the same indication. Developed by Ascendis Pharma using their TransCon technology platform.

Evidence & Sources

No sources recorded yet.