For adults with hypoparathyroidism who live on calcium and vitamin D tablets: what the longest follow-up of this daily hormone replacement found, and where the evidence still stops.
In a phase 3 trial at 21 sites in North America and Europe, 82 adults with hypoparathyroidism started on palopegteriparatide, a once-daily injection that replaces the missing parathyroid hormone and is approved in the US for adults with hypoparathyroidism, and 73 of them were still being followed three and a half years later. The 182-week results were published on 27 October 2026 in The Journal of Clinical Endocrinology & Metabolism by Khan, Rejnmark and colleagues from the PaTHway trial.
What the standard treatment cannot do
The four parathyroid glands in the neck make parathyroid hormone, which keeps the level of calcium in the blood steady. When the hormone is missing, calcium falls. The usual treatment is calcium tablets together with active vitamin D: they raise blood calcium, but, as the PaTHway investigators wrote, they do not restore normal parathyroid hormone physiology. Palopegteriparatide is designed to release the hormone steadily over 24 hours from one daily injection under the skin. A review published in Annals of Pharmacotherapy in October 2026 describes it as the only medicine approved by the US Food and Drug Administration that addresses the hormone deficiency itself.
The blinded half year
The trial started with 26 weeks in which neither participants nor doctors knew who was on the drug. Participants were randomised 3:1 to palopegteriparatide or a placebo injection, both on top of their usual tablets, which were reduced step by step according to blood calcium. The main goal combined three things: normal blood calcium, no active vitamin D and only a small amount of calcium, and no recent increase in the study drug. At week 26 this was reached by 79% of people on the drug (48 of 61) and 5% on placebo (1 of 21).
Three and a half years later
After week 26 everyone received the drug openly. At week 182, 96% of those still in the trial (70 of 73) no longer needed therapeutic calcium doses, all 73 were off active vitamin D, and 89% (65 of 73) had blood calcium within the normal range. Average calcium loss in the urine, above normal at the start, had normalised early and stayed that way, and the improvement in kidney filtration (eGFR) and in patient-reported symptoms seen in the first years was preserved. Markers of bone turnover rose and then settled above their starting values, and bone density moved towards the average for age and sex while remaining above it. Most side effects were mild or moderate.
Where the evidence stops
Only the first 26 weeks were randomised and blinded. The three-year extension had no comparison group, and everyone knew they were receiving the drug, so the long-term kidney, bone and quality-of-life findings are changes within the same people over time, not a difference against standard treatment. The trial was small, 82 people, and nine of them did not reach week 182; the published summary does not say why. The trial reported blood and urine calcium, kidney filtration, bone markers and density, symptoms and side effects; these data do not show an effect on fractures or kidney failure. The trial was sponsored by the manufacturer, Ascendis Pharma.
What to bring to the endocrinologist
For adults with long-term hypoparathyroidism who manage it with calcium and active vitamin D tablets, this is the longest published follow-up of palopegteriparatide, a hormone that replaces what the glands no longer make, and in most participants it kept blood calcium in range without that tablet regimen. Whether it suits a particular person, and how blood calcium and kidney function would be monitored during a switch, is worth discussing with your endocrinologist.
This article is for information only and does not replace a consultation with a doctor.
Sources
Khan AA, Clarke BL, Rubin MR, et al. Palopegteriparatide in Adults With Hypoparathyroidism: 3.5-Year Results From the Phase 3 PaTHway Trial. J Clin Endocrinol Metab, 2026, published online 27 October. PubMed 42935168, doi:10.1210/clinem/dgag440
Khan AA, Rubin MR, Schwarz P, 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. PubMed 36271471
Lewis L, Liu J, Sharma A, Yuan L. Palopegteriparatide: Parathyroid Hormone Analog for the Treatment of Chronic Hypoparathyroidism in Adults. Ann Pharmacother, 2026. PubMed 42924498
PaTHway trial registration: ClinicalTrials.gov NCT04701203
Articles in this section are educational and are not medical advice, a diagnosis, or a prescription. Consult a qualified professional before acting on anything you read here.
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