Palopegteriparatide
Also known as: Yorvipath, TransCon PTH, Palopegteriparatid, PTH(1-34) prodrug
Key Facts: Palopegteriparatide
- Category
- Hormonal
- FDA Status
- FDA Approved
- Clinical Status
- FDA Approved - Yorvipath (August 2024) for hypoparathyroidism in adults. Not studied in acute post-surgical hypoparathyroidism. Also approved in the EU, Australia and Switzerland. WADA: not on the 2026 Prohibited List.
- Banned in Sport (WADA)
- Not on the WADA Prohibited List (2026).
- Administration
- Subcutaneous injection once daily with a prefilled pen, using a single injection per dose
- Typical Dose
- 18 mcg once daily to start
- Frequency
- Once daily
- Duration
- Long-term, as chronic hormone replacement
How does Palopegteriparatide work?
Hypoparathyroidism means too little parathyroid hormone, so blood calcium runs low and patients live on big doses of calcium and active vitamin D. Palopegteriparatide is PTH(1-34) attached to a carrier (methoxypolyethylene glycol) through a linker that slowly breaks at body pH and temperature, releasing PTH(1-34) and its active metabolite PTH(1-33). Both act on the PTH1 receptor to raise calcium reabsorption in the kidney, activate vitamin D, and release calcium from bone. The key design point is steady exposure: the apparent half-life of released PTH is about 60 hours, so one daily injection gives near-physiological levels instead of the spike-and-crash of short-acting PTH. That is what lets patients drop active vitamin D and most calcium tablets.
What does the research show?
The pivotal PaTHway trial (NCT04701203) randomized 82 adults to palopegteriparatide (starting 18 mcg/day) or placebo for 26 weeks, both titrated against serum calcium. 68.9% on drug met the full composite endpoint (normal calcium, no active vitamin D, calcium 600 mg/day or less, stable dose) vs 4.8% on placebo. 95% got off active vitamin D vs 24% on placebo. Kidney function (eGFR) also improved during the blinded period. The label is honest about durability: strict responder rates fell to 39.3% at weeks 52 and 78 under the original definition, but when dose increases were allowed, 64-66% kept normal calcium without conventional therapy. Side effects were mostly injection site reactions (39%), dizziness and other low blood pressure symptoms (28%) and headache (21%). The FDA issued a complete response letter in 2023 over control of delivered dose from the pen, then approved it in August 2024. The label warns against splitting a dose into two injections because it makes delivered dose more variable. Outside the US it has EU approval, TGA registration in Australia (2025) and Swissmedic approval (December 2025).
FDA Approval Studies
This peptide is FDA approved. Below are the key clinical trials that supported its approval.
PaTHway
Ascendis Pharma • Phase 3
82
26 weeks blinded, then open-label extension
Normal serum calcium with independence from active vitamin D and therapeutic calcium at week 26
- ✓68.9% met composite endpoint vs 4.8% placebo
- ✓95.1% independent of active vitamin D vs 23.8%
- ✓86.9% off therapeutic calcium doses vs 4.8%
- ✓With dose titration allowed, 64-66% maintained response at weeks 52-78
What doses have been studied?
Typical Dosingⓘ
Community experience
18 mcg once daily to start
6-30 mcg once daily
Once daily
Dose is individualized by serum calcium, checked 7-10 days after each change. Active vitamin D and calcium supplements are reduced on the start day per the label. Use one injection per dose; two injections to reach a dose increase the risk of unexpected calcium swings.
Research Dosingⓘ
Scientific studies
FDA-approved labeled dosing (prescription only)
Doses from Studies
18 mcg once daily, adjusted in 3 mcg increments, max 30 mcg
FDA Approved Labeling - Yorvipath prescribing information (08/2024), sections 2.1 and 2.4 ↗
Starting 18 mcg/day, titrated over 26 weeks
Phase 3 RCT - PaTHway (NCT04701203), 82 adults with hypoparathyroidism ↗
Duration
Long-term, as chronic hormone replacement
Administration
Subcutaneous injection once daily with a prefilled pen, using a single injection per dose
When and how is Palopegteriparatide taken?
Best Time to Take
Same time each day
Once daily, single injection
Food Recommendation
With or without food
Why This Timing?
The released PTH has a half-life of about 60 hours, so levels stay steady and time of day matters less than consistency.
What are the side effects of Palopegteriparatide?
Not everyone experiences these effects. Individual responses vary based on dosage, duration, and personal factors.
- ●Injection site reactions (39%)
- ●Dizziness, palpitations, orthostatic hypotension (28%)
- ●Headache (21%)
- ●Diarrhea
- ●Back pain
- ●Hypercalcemia
- ●Hypocalcemia, especially when changing dose or stopping
- ●Oropharyngeal pain
- ●Potential osteosarcoma risk (rat data); not recommended for people at increased risk
- ●Digoxin toxicity risk if calcium rises
References
- https://www.accessdata.fda.gov/drugsatfda_docs/nda/2024/216490Orig1s000Lbl.pdf
- https://pharmacytimes.com/view/fda-approves-palopegteriparatide-for-treatment-of-hypoparathyroidism
- https://www.swissmedic.ch/swissmedic/en/home/humanarzneimittel/authorisations/new-medicines/yorvipath-injlsg-palopegteriparatidum.html
Research This Peptide Further
Frequently Asked Questions
What does Palopegteriparatide do?
Palopegteriparatide is a long-acting prodrug of PTH(1-34), the active part of parathyroid hormone, built so that it releases steady hormone levels around the clock. Sold as Yorvipath by Ascendis Pharma, it was FDA approved in August 2024 as the first treatment specifically for hypoparathyroidism in adults, after a 2023 rejection over dose-delivery issues with the pen. With Natpara now gone, it is the main hormone replacement option for this condition, and the trial results are genuinely strong.
How does Palopegteriparatide work?
Hypoparathyroidism means too little parathyroid hormone, so blood calcium runs low and patients live on big doses of calcium and active vitamin D. Palopegteriparatide is PTH(1-34) attached to a carrier (methoxypolyethylene glycol) through a linker that slowly breaks at body pH and temperature, releasing PTH(1-34) and its active metabolite PTH(1-33). Both act on the PTH1 receptor to raise calcium reabsorption in the kidney, activate vitamin D, and release calcium from bone. The key design point is steady exposure: the apparent half-life of released PTH is about 60 hours, so one daily injection gives near-physiological levels instead of the spike-and-crash of short-acting PTH. That is what lets patients drop active vitamin D and most calcium tablets.
Is Palopegteriparatide FDA approved?
Yes, Palopegteriparatide is FDA approved. FDA Approved - Yorvipath (August 2024) for hypoparathyroidism in adults. Not studied in acute post-surgical hypoparathyroidism. Also approved in the EU, Australia and Switzerland. WADA: not on the 2026 Prohibited List.
Is Palopegteriparatide banned in sport?
Not on the WADA Prohibited List (2026).
What are the side effects of Palopegteriparatide?
Reported side effects include: Injection site reactions (39%), Dizziness, palpitations, orthostatic hypotension (28%), Headache (21%), Diarrhea, Back pain. Individual responses vary based on dosage, duration, and personal health factors.
What is the typical dose of Palopegteriparatide?
Community-reported common dose: 18 mcg once daily to start (Once daily). Range: 6-30 mcg once daily. Administration: Subcutaneous injection once daily with a prefilled pen, using a single injection per dose. Prescription drug. Dose set by prescriber per label. Not medical advice.
Related Peptides
Peptides commonly compared with Palopegteriparatide or used in similar applications.
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