What it is
Palopegteriparatide is a 34-amino-acid peptide on a slow-release carrier. The peptide is PTH(1-34) — the first 34 residues of the body's 84-residue parathyroid hormone, the stretch the Yorvipath label calls "the biologically active region." It is the same peptide sold on its own as teriparatide. Here it is "transiently conjugated" through Ascendis Pharma's TransCon linker to a branched 40 kDa methoxypolyethylene glycol (two 20 kDa arms). The whole molecule averages about 47.4 kDa; its formula is C209H340N60O59S3 plus the polyethylene glycol, 2 × (C2H4O)n with n of about 450 to 500 (label).
That makes it a prodrug: the carrier holds the peptide in the body, and the linker releases free PTH(1-34) over time. The point is a steadier hormone level from one injection a day, closer to how the glands themselves work than the short pulse a daily teriparatide injection gives.
The arithmetic, our reading of the label: each mL holds 3,456 mcg of palopegteriparatide and is "equivalent to 300 mcg of teriparatide." The peptide is therefore about 8.7% of the mass; the rest is carrier and linker. The pen sizes follow the same ratio — 1,935 mcg of the prodrug for 168 mcg of teriparatide in the smallest pen.
How it works
Parathyroid hormone holds blood calcium in a narrow range by acting on bone and kidney through the PTH1 receptor. In hypoparathyroidism the glands make too little of it — in 85% of the trial's participants, because the glands were damaged or removed in neck surgery. Without treatment calcium falls; the conventional answer is large doses of calcium and active vitamin D, which raise blood calcium but also the calcium passing into urine. Palopegteriparatide supplies the missing hormone's active fragment instead.
What the label's trial shows
The approval rests on one 26-week, randomised, double-blind, placebo-controlled phase 3 trial (NCT04701203, 82 adults, mean age 49, 78% women). Everyone stayed on calcium and active vitamin D at the start, and both were reduced as blood calcium allowed.
| Measure at week 26 | Yorvipath (61) | Placebo (21) |
|---|---|---|
| Composite endpoint met | 42 (68.9%) | 1 (4.8%) |
| Blood calcium in the normal range | 49 (80.3%) | 10 (47.6%) |
| Free of active vitamin D | 58 (95.1%) | 5 (23.8%) |
| Calcium supplement 600 mg/day or less | 53 (86.9%) | 1 (4.8%) |
| No dose increase since week 22 | 57 (93.4%) | 12 (57.1%) |
The difference on the composite endpoint was 64.2% (95% CI 49.5–78.8%). What the trial did not measure is the long-term complications of the disease — kidney stones, kidney function over years, cataracts. The label also limits the titration scheme to adults who had first reached a corrected calcium of at least 7.8 mg/dL on conventional therapy.
Safety
The label's warnings are hypersensitivity (anaphylaxis, angioedema and hives have been reported with PTH analogues), serious hypercalcaemia and hypocalcaemia, a potential risk of osteosarcoma — the bone tumour seen in rats given teriparatide, which is why it is not recommended for people at raised risk — orthostatic hypotension, and digoxin toxicity if calcium rises in someone taking digoxin. It also warns against splitting a dose across two injections, because that makes the delivered amount more variable. The dose is set and changed by the treating clinician against blood calcium measurements.
Where it stands
- Approved in the US on 2024-08-09 (Yorvipath, NDA 216490, Ascendis Pharma Bone), prescription only (Drugs@FDA, 2026-10-22). The current label is effective 2026-08-12.
- Research record: PubMed indexes 56 records for palopegteriparatide or TransCon PTH, 10 tagged as randomised controlled trials; ClinicalTrials.gov lists 11 studies (2026-10-22).
Related reading
The full hormone this drug borrows from is in the library's entry on parathyroid hormone and the PTH blood test. The same 34-residue peptide without a carrier, used for osteoporosis, is teriparatide (Forteo); a related bone drug built on the PTH-related protein is abaloparatide, built on PTHrP. An approved drug built the same way — peptides doing the binding, polyethylene glycol most of the mass — is pegcetacoplan. For where a 34-residue chain sits on the peptide–protein line, see peptide vs protein.