Yorvipath
Evidence Grade A — Regulatory approved. 32 published studies. 7 registered clinical trials.
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Palopegteriparatide (sold as Yorvipath) is the first and only hormone replacement therapy for hypoparathyroidism — a condition where the parathyroid glands do not produce enough hormone to regulate calcium, leaving patients dependent on high doses of calcium supplements and vitamin D just to maintain safe blood calcium levels. Given as a single daily injection, it slowly releases parathyroid hormone throughout the day.
32 published studies: 19 human, 0 animal, 0 in-vitro, 12 reviews
Palopegteriparatide is marketed as Yorvipath (Ascendis Pharma, approved August 2024). It is the first FDA-approved PTH replacement therapy for hypoparathyroidism, a condition that previously had no approved hormone replacement and was managed only with high doses of calcium supplements and active vitamin D — an approach that does not fully normalise calcium metabolism.
In the PaTHway trial, 79% of patients achieved independence from calcium and active vitamin D supplements while maintaining normal blood calcium levels, compared to 5% on placebo. This represents a fundamental shift in managing hypoparathyroidism — from supplementation to actual hormone replacement. Patients also showed improvements in kidney function markers and bone metabolism parameters.
Palopegteriparatide is a prodrug: the active parathyroid hormone fragment (PTH 1-34) is attached to a large carrier molecule (PEG) via a chemical linker that slowly breaks down at body temperature and pH. This gradually releases the active hormone over 24 hours, mimicking the continuous parathyroid hormone production that patients with hypoparathyroidism lack. The released PTH then regulates calcium and phosphorus metabolism through the same pathways as the body's natural hormone.
In the PaTHway trial, 79% of patients on palopegteriparatide achieved independence from calcium and active vitamin D supplements while maintaining normal blood calcium levels, compared to just 5% on placebo. This represents a fundamental shift from managing symptoms to actually replacing the missing hormone — comparable to how insulin replacement transformed diabetes care. Before Yorvipath, there was no dedicated treatment for hypoparathyroidism. The conventional approach (high-dose calcium and active vitamin D) does not restore normal calcium metabolism and carries risks of kidney damage from excessive calcium excretion. The hypoparathyroidism population is relatively small (approximately 70,000 diagnosed patients in the US). Post-marketing surveillance is monitoring long-term effects on bone health and kidney function.
Expanded Access Program of Palopegteriparatide in Patients With Hypoparathyroidism
A Phase 3 Randomized Clinical Trial to Investigate the Safety and Efficacy of Palopegteriparatide at Doses Greater Than 30 μg/Day in Adult Participants With Hypoparathyroidism
A Global Pregnancy Registry to Assess Maternal, Fetal, and Infant Outcomes Following Exposure to YORVIPATH® (Palopegteriparatide) During Pregnancy and Breastfeeding
A Study to Assess the Amount of Palopegteriparatide in Breast Milk of Lactating Females Requiring YORVIPATH® (Palopegteriparatide)
Translation and Validation of the Hypoparathyroidism Patient Experience Scales (HPES) Questionnaire in Greek
EMA Marketing Authorisation
FDA ORIG 1
FDA SUPPL 5
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