Palopegteriparatide (Yorvipath)_Dosage, benefits & legal status
Also known as Yorvipath, TransCon PTH, TransCon PTH (1-34), TransCon parathyroid hormone (1-34), ACP-014, mPEG 40000-teriparatide
Teriparatide tethered to a large PEG carrier through a linker that lets it go slowly, so one daily injection gives steady hormone levels. In the pivotal trial 68.9% met the FDA's goal against 4.8% on placebo.
Common vial size is what vendors typically sell, not a recommendation. Enter your own vial in the calculator.
What is Palopegteriparatide (Yorvipath)?
Plain language first. The technical label stays, but it never stands alone.Overview
When the parathyroid glands stop working, often after neck surgery (85% of trial patients), blood calcium falls and people depend on daily calcium and active vitamin D pills. In the 26-week PaTHway trial, 68.9% on palopegteriparatide (42 of 61) had normal calcium without active vitamin D or therapeutic calcium on a stable dose, by the FDA's definition, against 4.8% (1 of 21) on placebo. Blood calcium can still swing too high or too low, especially when starting, raising the dose or stopping suddenly, so the dose is adjusted to blood tests.
Palopegteriparatide is a prodrug of teriparatide, PTH(1-34): the 34-residue peptide is attached at its N-terminal amine through Ascendis Pharma's TransCon linker to a branched 40 kDa (2 x 20 kDa) methoxypolyethylene glycol carrier, and it is inactive until the linker releases it. Released PTH(1-34) acts on PTH1 receptors in kidney and bone with an apparent half-life of about 60 hours, giving steady exposure from one daily injection instead of the short daily pulse of teriparatide (Forteo) used to build bone in osteoporosis. Canvuparatide, an investigational 32-residue PTH-based peptide, is a separate molecule.
What it's used for
A once-daily injection under the skin from a prefilled pen, to replace missing parathyroid hormone in adults with hypoparathyroidism.
How does Palopegteriparatide (Yorvipath) work?
What it does in the body, and where.Palopegteriparatide is teriparatide on a slow-release tether, built to replace the parathyroid hormone the body no longer makes.
- 01The missing hormoneParathyroid hormone acts on PTH1 receptors in the kidney and bone: the kidney holds on to calcium, excretes more phosphate and makes more active vitamin D, and bone releases calcium. Without it, blood calcium falls and people rely on calcium and active vitamin D pills.
- 02An inactive carrierEach daily injection deposits PTH(1-34) joined through the TransCon linker to a large branched PEG carrier. While attached it is inactive; under normal body conditions the linker slowly releases free PTH(1-34).
- 03Steady levelsPTH peaks about 4 hours after a dose, and the released hormone has an apparent half-life of about 60 hours, so levels stay steady and plateau after 7 days of daily dosing. Teriparatide injected on its own gives a short daily spike, the pattern used to build bone in osteoporosis.
A schematic of the compound's mechanism, not a diagnostic image.
What else is it used for?
Each group carries its own evidence level.Approved means regulators have cleared it for that purpose. Investigational means it is in trials. Early research means it is being studied and is not established.
Pivotal trial (PaTHway)
FDA-approved- Human trial84 randomized: 79% (48 of 61) against 5% (1 of 21) met the protocol's primary endpoint at 26 weeks (p<0.0001). The label's stricter FDA analysis of the same trial gives 68.9% against 4.8%.
- Human trialAll key domain scores of the Hypoparathyroidism Patient Experience Scale improved against placebo (all p<0.01); SF-36 physical functioning p=0.0347.
- Human trialAny adverse event in 82% (50 of 61) against 100% (21 of 21), with no withdrawals for drug-related reasons.
Phase 2 (PaTH Forward)
FDA-approved- Human trial59 adults: by week 26, 91% were free of standard care (no active vitamin D and 500 mg of calcium a day or less); mean 24-hour urine calcium fell from 415 to 178 mg (44 patients); no treatment-related serious or severe adverse events.
Longer-term results
FDA-approved- Human trialBy the strict FDA definition, 39.3% (24 of 61) still responded at weeks 52 and 78; with dose increases allowed, 64% at week 52 and 66% at week 78 had normal calcium without active vitamin D or therapeutic calcium.
China (PaTHway China)
Investigational- Human trial81 adults randomized 3:1: 77.6% (45 of 58) against 0 of 22 had normal calcium without conventional therapy at week 26 (p<0.0001). A journal publication is not established.
Safety signals
FDA-approved- Animal studyRats given PTH drugs developed osteosarcoma; the label carries this as a standard warning, not a boxed one.
- No dataAnti-PEG antibodies developed in 5% (7 of 139); 3 people with anti-PEG antibodies before treatment had transient effects on drug levels and calcium. Anti-PTH antibodies appeared in 0.7% (1 of 139).
- RegulatoryTwo injections a day make the delivered dose less predictable, so the label allows only one.
The pivotal result circulates in two versions. The label's 68.9% (42 of 61) against 4.8% (1 of 21), often quoted as 69% against 5%, uses the FDA's stricter definition, adding a dose of 30 mcg or less, no missing data and week-22 timing; the published primary endpoint was 78.7% (48 of 61) against 4.8%. Trial size is quoted as 82 or 84: 84 were randomized and 82 dosed. The FDA's trial snapshot gives the maximum dose as '30 mg'; it is 30 mcg. The 60-hour half-life is the apparent half-life of PTH released from the prodrug, not of PTH(1-34) itself. Doses and pen strengths are teriparatide equivalents; the conjugate weighs about 11.5 times more (3,456 mcg of palopegteriparatide carries 300 mcg of teriparatide). GSRS gives 4,120 Da, a figure that leaves out the 40 kDa PEG; the whole molecule averages about 47.4 kDa. The released peptide has the same sequence as teriparatide (Forteo), but it has not been studied for osteoporosis. Canvuparatide (MBX 2109) is also an investigational PTH prodrug, but it is a different molecule from a different company (MBX Biosciences), a 32-residue PTH-based peptide designed for once-weekly dosing, and the two should not be assumed to share a platform. The osteosarcoma language is a standard warning, not a boxed one. The PaTHway paper is sometimes dated 2020; it appeared in J Bone Miner Res 2023;38:14-25.
The published record
Papers and trials about Palopegteriparatide (Yorvipath)
42 papers tagged human · 22 not reviews or lab · 11 clinical trial publications
11 registered trials · 2 with posted results
Furthest stage reached: Approved in the US
Counted from Europe PMC indexing, not read by a person; a human tag can land on reviews, commentary or lab papers; clinical trial publications is the narrower count.
At a glance
Four things to know about Palopegteriparatide (Yorvipath)
Evidence
FDA-approved
Category
Healing and recovery
Common vial
Varies
Half-life
About 60 hours (apparent, for PTH released from the prodrug)
How much, and do you cycle it?
The range, and whether you take breaks.18 mcg once daily to start, adjusted within 6 to 30 mcg (label), once daily. Continuous, once daily FDA label
Replacement for a chronic hormone deficiency; serious low calcium is most likely after stopping suddenly.
How long does it stay in the body?
The half-life, and where the figure comes from.About 60 hours (apparent, for PTH released from the prodrug)FDA label
PTH peaks a median 4 hours after a dose (range 4 to 8) and reaches steady state after 7 days of daily dosing. Clearance at steady state 0.58 L a day; volume of distribution 4.8 L. Mild, moderate or severe kidney impairment had no clinically significant effect on exposure. Released PTH includes PTH(1-34) and an active metabolite, PTH(1-33), with comparable PTH1 receptor activity; how the carrier is eliminated is not described in the label.
Source: Yorvipath US prescribing information, section 12.3
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How is it given?
Dosing context and source notes.Supplied as a pen or prefilled syringe, so there is nothing to mix.
Label range: 6 up to 30 mcg per day. Yorvipath US prescribing information (DailyMed, revised August 2026), sections 2 and 16
One injection under the skin each day, starting at 18 mcg and adjusted by 3 mcg at a time against albumin-corrected blood calcium: up no more often than every 7 days, down no more often than every 3 days, within 6 to 30 mcg a day. Only one injection a day is used, because splitting a dose makes the delivered amount less predictable. Doses are teriparatide equivalents. Supplied as three prefilled pens: 168 mcg/0.56 mL delivers 6, 9 or 12 mcg, 294 mcg/0.98 mL delivers 15, 18 or 21 mcg, and 420 mcg/1.4 mL delivers 24, 27 or 30 mcg. Each pen gives 14 daily doses; pens are refrigerated at 2 to 8°C before first use, then kept below 30°C and discarded after 14 days. A dose missed by more than 12 hours is skipped; after a break of 3 days or more, the label says to check for signs of low calcium and consider a calcium test, resume the previous dose as soon as possible, and measure calcium within 7 to 10 days. No adjustment is needed for kidney impairment down to an eGFR of 15. There is nothing to mix from powder.
How do you store it?
Before mixing, and after.Supplied ready to use. Store it as the label says.
Palopegteriparatide (Yorvipath) comes as a ready-made solution, prefilled syringe or ampoule, not a powder, so there is no mixing step and no reconstitution clock. Keep it in its original pack and follow the storage and expiry dates on the label. Many ready-made peptide medicines are kept in the fridge and must not be frozen; a few are made to be stored at room temperature.
What are the side effects and cautions?
Known cautions and warnings for this compound.Solubility, computed: 32% charged residues, 38% hydrophobic. Water usually sufficient.
A first-pass rule from peptide manufacturers' guidance. It does not account for disulfide bridges, salt form or how the powder was dried, and it predicts what should be easy rather than what will happen in your vial.
Who should avoid it
- A history of severe allergic reaction to palopegteriparatide or any of its inactive ingredients (the only label contraindication)
- Increased risk of osteosarcoma, a bone cancer seen in rats given PTH drugs: the label says it is not recommended (a warning, not a boxed warning)
- Not studied in acute hypoparathyroidism right after surgery
Stop and get help
- Hives, swelling of the face or throat, or trouble breathing, possible severe allergic reaction: the label says to stop permanently after a severe reaction
- Albumin-corrected calcium of 12 mg/dL or higher: the label says to hold doses for 2 to 3 days and recheck
Common effects
- Injection-site reactions in 39% against 5% on placebo over 26 weeks (61 against 21 patients)
- Vasodilatory signs and symptoms in 28% against 0%, and headache in 21% against 10%
- Diarrhea 10% against 5%, back pain 8% against 0%, symptomatic high calcium 8% against 0% (all in the first 3 months) and mouth and throat pain 7% against 0%
- Albumin-corrected calcium above 10.6 mg/dL at some point in 54.1% against 9.5%, and above 12 mg/dL in 13.1% against 0%
Where this page says nothing is established, that means nobody has studied it, not that a compound is safe.
Is Palopegteriparatide (Yorvipath) approved?
And where the numbers on this page come from.Yes. Palopegteriparatide (Yorvipath) is FDA approved and available on prescription in the United States. It is also approved in the European Union, the United Kingdom, and Japan.
- Approval statusFDA-approved
- RouteUnder the skin (prefilled pen)
- Checked17 October 2026
- Approved outside the USEuropean Union, United Kingdom, Japan: EU marketing authorization on November 17, 2023 (EMEA/H/C/005934) for adults with chronic hypoparathyroidism. The MHRA approved it for the same use in Great Britain in 2024. In Japan, Teijin Pharma filed on December 13, 2024, and Ascendis reported a milestone tied to the Japanese approval in the third quarter of 2025 (exact date not established); Teijin launched it in Japan on November 6, 2025. Ascendis reported Yorvipath available commercially or through named-patient programs in more than 35 countries by mid-2026. Approval in China is not established; VISEN's phase 3 there met its primary endpoint in 2024.This does not change the United States position above.
- DoseFrom the drug label. The manufacturer tested this range and a regulator reviewed it.
- Vial sizeFrom what vendors typically list; not a recommendation.
- SourcesYorvipath US prescribing information (DailyMed, revised August 2026)Drugs@FDA, NDA 216490FDA Drug Trials Snapshot, YorvipathFDA GSRS substance record, palopegteriparatide (UNII G2N64C3385)EMA, Yorvipath EPARKhan AA et al., Journal of Bone and Mineral Research 2023;38:14-25 (PaTHway)ClinicalTrials.gov, PaTHway (NCT04701203)Khan AA et al., Journal of Clinical Endocrinology & Metabolism 2022;107:e372-e385 (PaTH Forward)Ascendis Pharma, Form 6-K on the complete response letter (May 2023)Ascendis Pharma, US commercial availability (December 19, 2024)Ascendis Pharma, third quarter 2025 resultsMarketBeat, Ascendis Pharma second quarter 2026 earnings callPharma Japan (Jiho), Teijin filing in JapanVISEN Pharmaceuticals, PaTHway China results (via Synapse)
What has happened recently
The EU authorized Yorvipath (Ascendis Pharma Bone Diseases A/S) on November 17, 2023, for adults with chronic hypoparathyroidism, after orphan designation on October 19, 2020; Germany and Austria launched first. In the US, a complete response letter announced on May 1, 2023, cited the manufacturing control strategy for variability in the dose the pen delivers, without asking for new trials; the FDA then approved NDA 216490 on August 9, 2024, as a new molecular entity with priority review and orphan designation. Ascendis announced US prescription availability on December 19, 2024; at approval it had said it was still completing commercial manufacturing for the US market. The August 2026 label added a warning on hypersensitivity reactions. Teijin Pharma filed in Japan on December 13, 2024, and Ascendis reported a milestone tied to the Japanese approval in the third quarter of 2025; VISEN Pharmaceuticals holds Greater China rights and targeted a China filing for the end of 2025, but in January 2026 it was still preparing to file. A trial of doses up to 60 mcg a day is under way, and an adolescent trial was planned to start in late 2025. There are no generics.
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What else is like Palopegteriparatide (Yorvipath)?
Others in Healing and recovery, side by side.If you're weighing Palopegteriparatide (Yorvipath), it's worth reading Pentosan Polysulfate (PPS), Plecanatide (Trulance), and Redasemtide in the same class.
Teriparatide tethered to a large PEG carrier through a linker that lets it go slowly, so one daily injection gives steady hormone levels. In the pivotal trial 68.9% met the FDA's goal against 4.8% on placebo.
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Guides for this compound
- How to Reconstitute a Peptide
Mix peptide powder with bacteriostatic water, step by step.
- How to Read an Insulin Syringe
Read the units, convert to millilitres, and draw the exact dose.
- mcg vs mg: The Peptide Dosing Mistake to Avoid
Your vial says mg and your protocol says mcg. Here is the conversion and how to check it.
Sources
- Yorvipath US prescribing information (DailyMed, revised August 2026)(2026)Adults with hypoparathyroidism; 18 mcg start, 6 to 30 mcg a day; adverse reaction table; apparent half-life about 60 hours; 68.9% against 4.8% on the FDA endpoint.
- Drugs@FDA, NDA 216490(2026)Approved August 9, 2024: new molecular entity, priority review, orphan; supplements October 16, 2025 and August 3, 2026; three pen strengths.
- FDA Drug Trials Snapshot, Yorvipath(2024)82 patients in the pivotal trial, 30 from the US; gives the maximum dose as '30 mg', an error for 30 mcg.
- FDA GSRS substance record, palopegteriparatide (UNII G2N64C3385)(2026)CAS 2222514-07-8; codes ACP-014 and TransCon PTH; human PTH(1-34) joined at its N-terminal amine through a cleavable linker to 2 x 20 kDa mPEG.
- EMA, Yorvipath EPAR(2023)EU authorization November 17, 2023 (EMEA/H/C/005934) for adults with chronic hypoparathyroidism; orphan designation October 19, 2020.
- Khan AA et al., Journal of Bone and Mineral Research 2023;38:14-25 (PaTHway)(2023)Protocol primary endpoint 79% (48 of 61) against 5% (1 of 21), p<0.0001; quality-of-life domains improved (all p<0.01).
- ClinicalTrials.gov, PaTHway (NCT04701203)(2025)84 randomized, 82 dosed; primary endpoint 78.7% against 4.8%; results posted February 28, 2025.
- Khan AA et al., Journal of Clinical Endocrinology & Metabolism 2022;107:e372-e385 (PaTH Forward)(2022)Phase 2, 59 adults: 91% free of standard care at week 26; urine calcium fell from 415 to 178 mg a day.
- Ascendis Pharma, Form 6-K on the complete response letter (May 2023)(2023)Letter announced May 1, 2023, over manufacturing control of delivered-dose variability; no new clinical trials requested.
- Ascendis Pharma, US commercial availability (December 19, 2024)(2024)Yorvipath available by prescription in the US.
- Ascendis Pharma, third quarter 2025 results(2025)More than 4,250 US patient enrollments by September 30, 2025; milestone tied to the Japanese approval; PaTHway60 and adolescent trials.
- MarketBeat, Ascendis Pharma second quarter 2026 earnings call(2026)Yorvipath revenue EUR 252 million in the quarter; about 1,000 new US enrollments a quarter; available commercially or through named-patient programs in more than 35 countries.
- Pharma Japan (Jiho), Teijin filing in Japan(2024)Japanese application filed December 13, 2024.
- VISEN Pharmaceuticals, PaTHway China results (via Synapse)(2024)81 adults: 77.6% (45 of 58) against 0 of 22 on the primary endpoint at week 26, p<0.0001.
Beyond these, 72 records are indexed. Browse the records