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Evidence: HighPeptide conjugateFDA ApprovedPTH(1-34) prodrugFDA-approved · YorvipathHypoparathyroidism

Palopegteriparatide

A once-daily prodrug that releases parathyroid hormone steadily, for adults whose glands no longer make enough

Palopegteriparatide is PTH(1-34), the active fragment of parathyroid hormone, bound to an inert carrier that releases it steadily. Approved as Yorvipath in 2024 for hypoparathyroidism in adults, it let most trial participants stop active vitamin D and high-dose calcium.

At a Glance Read Research →
Overview

What is it?

In hypoparathyroidism the parathyroid glands make too little hormone, so blood calcium falls. Calcium and active vitamin D relieve that but do not restore normal parathyroid hormone physiology. Palopegteriparatide replaces the hormone itself: PTH(1-34) bound to an inert carrier and designed to release it steadily.

In the phase 3 PaTHway trial, 84 adults were randomized three to one to the drug or placebo. At 26 weeks, 79% on the drug met the main goal against 5% on placebo. At one year, 81% had normal blood calcium without conventional therapy and none needed active vitamin D; at two years, 97% of those still taking it were independent of conventional therapy.

Yorvipath was approved in the US on August 9, 2024, for adults; it was not studied in the acute form straight after surgery. The dose follows blood calcium, checked 7 to 10 days after each change, and is always one injection, because two make the dose more variable.

Structured data

At a Glance

Every value in this table is printed from the Grey Peptides dataset, the same record the compound explorer and comparison tool read, so the three can never disagree.

ClassA prodrug of PTH(1-34), the active fragment of parathyroid hormone, transiently bound to an inert carrier so that it is released steadily; FDA-approved as Yorvipath for hypoparathyroidism in adults.
SequenceSVSEIQLMHNLGKHLNSMERVEWLRKKLQDVHNF (PTH(1-34), the fragment released from the carrier)
Half-lifeabout 60 hours for the PTH released from the prodrug
Label dose18 mcg (once daily, subcutaneous)
US statusFDA Approved
Evidence levelHigh
Last reviewed2026-10-02

Educational information, not medical advice. The doses on this page come from approved labels, published studies and, where no study exists, amounts reported by users. None is a recommendation for you. An unapproved compound has no established safe or effective human dose, and products sold for “research use only” are not made or tested for people. Talk to a doctor before acting on anything on this site, including before you start, stop or change any medicine or dose. Full medical disclaimer.

Interactive

Half-Life: How Much Remains

The dataset records a half-life of about 60 hours for the PTH released from the prodrug for Palopegteriparatide. After each half-life, half of what was in the circulation is gone, so about 3% remains after five. Real clearance varies with the person, the dose, the route and kidney or liver function; this is arithmetic on a published figure, not a dosing tool.

Time since a single dose
ElapsedTimeRemaining
1 half-life2.5 days50% remaining
2 half-lives5 days25% remaining
3 half-lives7.5 days12.5% remaining
4 half-lives10 days6.25% remaining
5 half-lives12.5 days3.125% remaining
Evidence

Published Research

The studies behind palopegteriparatide, read from their PubMed abstracts.

Human2022

PaTH Forward: phase 2, 59 adults

Adults with hypoparathyroidism took 15, 18 or 21 µg a day or placebo for four weeks, then an adjusted dose of 6 to 60 µg a day. By week 26, 91% of those on the drug no longer needed active vitamin D and took 500 mg or less of calcium a day.

PMID: 34347093
Human2023

PaTHway: phase 3, 26 weeks, 84 adults

Adults were randomized three to one to the drug, starting at 18 µg a day, or placebo. At week 26, 79% on the drug met the composite primary goal, which required normal blood calcium, against 5% on placebo; 93% no longer needed conventional therapy. Adverse events: 82% against 100%, mostly mild or moderate.

PMID: 36271471
Human2025

PaTHway at one year

Of 82 adults who received the drug, 78 completed week 52. At week 52, 81% had normal blood calcium without conventional therapy, 95% were independent of conventional therapy, and none needed active vitamin D.

PMID: 39376010
Human2026

PaTHway at two years: kidney function

At week 104, 76 of 82 remained in the open-label extension; 82% of them had normal blood calcium and 97% were independent of conventional therapy. This post hoc analysis reported sustained improvement in eGFR, a measure of kidney filtration.

PMID: 42166177
Human2025

Case report: stopping after three years

A 62-year-old man with hypoparathyroidism after surgery stopped the drug after three years and restarted calcium and calcitriol at adjusted doses. The report describes a rebound effect after stopping.

PMID: 40956444
Safety

Side Effects & Contraindications

Reported Side Effects

From the trials above.

● Adverse events were common in both groups in PaTHway, 82% on the drug and 100% on placebo, mostly mild or moderate
● A case report describes a rebound effect after stopping the drug

Contraindications & Cautions

From the Yorvipath label (DailyMed, effective August 12, 2026).

● A previous severe allergic reaction: the label says to stop permanently
● Two injections to make up one dose, which makes the delivered dose more variable
● Use without regular blood calcium checks: serious high and low calcium have occurred
● Tested athletes — see the Sport (WADA) row below
Questions

Frequently Asked Questions

?What is palopegteriparatide?

A once-daily prodrug of PTH(1-34), the active fragment of parathyroid hormone, bound to a carrier that releases it steadily. It is sold in the US as Yorvipath for hypoparathyroidism in adults.

?How is it different from teriparatide?

Both deliver PTH(1-34). Teriparatide is a brief daily pulse for osteoporosis; palopegteriparatide releases it steadily, the released hormone lasting about 60 hours, to replace what is missing.

?What dose is used?

The label starts at 18 micrograms once daily and adjusts in 3 microgram steps by blood calcium, to a maximum of 30 micrograms, always as a single injection.

?What happens if it is stopped?

A 2025 case report describes a rebound effect after stopping; the label warns that serious high and low blood calcium have occurred.

Bibliography

References

  1. [fda] FDA. Drugs@FDA (openFDA): YORVIPATH (palopegteriparatide) injection, NDA 216490, original approval August 9, 2024, prescription. Read October 2, 2026.
  2. [fda] FDA. Yorvipath (palopegteriparatide) injection US prescribing information (DailyMed set a1fa23fd-c434-443e-9a17-5750578c8602, effective August 12, 2026). Read October 2, 2026.
  3. [clinical-trial] Khan AA, et al. "PaTH Forward: A Randomized, Double-Blind, Placebo-Controlled Phase 2 Trial of TransCon PTH in Adult Hypoparathyroidism." J Clin Endocrinol Metab, 2022;107(1):e372-e385. PMID: 34347093.
  4. [clinical-trial] Khan AA, et al. "Efficacy and Safety of Parathyroid Hormone Replacement With TransCon PTH in Hypoparathyroidism: 26-Week Results From the Phase 3 PaTHway Trial." J Bone Miner Res, 2023;38(1):14-25. PMID: 36271471.
  5. [clinical-trial] Clarke BL, et al. "Efficacy and Safety of TransCon PTH in Adults With Hypoparathyroidism: 52-Week Results From the Phase 3 PaTHway Trial." J Clin Endocrinol Metab, 2025;110(4):951-960. PMID: 39376010.
  6. [pubmed] Rejnmark L, et al. "Sustained improvement in renal function with palopegteriparatide in adults with chronic hypoparathyroidism: 2-year results from the phase 3 PaTHway-trial." J Bone Miner Res, 2026;41(9):922-933. PMID: 42166177.
  7. [pubmed] Naciu AM, et al. "Rebound Effect Following the Discontinuation of Palopegteriparatide." Calcif Tissue Int, 2025;116(1):121. PMID: 40956444.
  8. [pubmed] Karpf DB, et al. "A Randomized Double-Blind Placebo-Controlled First-In-Human Phase 1 Trial of TransCon PTH in Healthy Adults." J Bone Miner Res, 2020;35(8):1430-1440. PMID: 32212275.

Sources & Citations

Studies were read from their PubMed records; regulatory sources are listed below, read October 2, 2026.

Medical Disclaimer: This content is for educational and informational purposes only. It is not medical advice, and nothing here is an instruction to obtain or use any compound. Consult a licensed healthcare provider before making health decisions.

Last reviewed: 2026-10-02