Ascendis Pharma TransCon PTH sustains efficacy at 3.5 years in Phase 3
Ascendis Pharma has published Week 182 data from its completed Phase 3 PaTHway Trial, reporting that TransCon PTH (palopegteriparatide) sustained efficacy and safety over three and a half years in adults with hypoparathyroidism. The Copenhagen-headquartered company said the prodrug replicated the systemic actions of endogenous parathyroid hormone across four primary target organ systems: the central nervous system, kidneys, small intestine, and bone.
The trial enrolled 82 adults, of whom 89% completed the full duration. Eighty-six per cent of patients met the trial's multi-component response endpoint, defined as serum calcium within the normal range, no active vitamin D supplementation, and calcium intake of no more than 600 mg per day. All patients achieved independence from active vitamin D by Week 182, and 96% achieved independence from therapeutic calcium doses.
Clinical data
Kidney function outcomes were among the most striking findings. Mean estimated glomerular filtration rate at Week 182 was 80.2 mL/min/1.73 m², reflecting a mean increase of 11.0 mL/min/1.73 m² from baseline. Ascendis noted this trajectory contrasts with the expected age-related eGFR decline in adults, citing a 2024 study in BMJ Open. The improvement was observed both in patients who received TransCon PTH throughout and in those who crossed over from placebo at Week 26, with eGFR stabilising after Week 38 and remaining stable thereafter.
Bone mineral density Z-scores, elevated at baseline, corrected towards normal through Week 26 and remained above 0 through Week 182. Twenty-four-hour urine calcium normalised within 26 weeks and held stable. Patient-reported outcomes on the Hypoparathyroidism Patient Experience Scales and the SF-36 instrument showed sustained gains across all domains, including physical functioning, cognitive symptoms, and daily-life impact.
Aimee Shu, chief medical officer at Ascendis Pharma, said the drug had "normalised key biochemistries and skeletal health while significantly improving kidney function and quality of life beginning at the earliest timepoints and continuing through multiple years of treatment." The safety profile was described as consistent with earlier data: adverse events were predominantly mild or moderate, there were no discontinuations attributed to the study drug, and no patients developed anti-PTH antibodies over the course of the trial.
Market context
TransCon PTH is already approved under the brand name YORVIPATH in the United States, the European Union, and several other jurisdictions as a treatment for adult hypoparathyroidism, making the Week 182 dataset a commercial-stage evidence dossier rather than a pivotal regulatory filing. The condition affects an estimated 70,000 to 90,000 adults in the United States alone, the majority of whom develop it following parathyroid gland damage during thyroid or neck surgery.
The long-term dataset strengthens Ascendis's position in what remains a thinly served endocrine indication. Conventional management relies on calcium and active vitamin D supplementation, an approach that carries chronic risks of hypercalciuria and renal impairment. Natpara (rhPTH 1-84, from Takeda) holds US approval in the same indication but has faced recurring supply constraints; no other approved PTH replacement is available in major markets at present. The durability of eGFR improvement shown in PaTHway, if it informs label updates or real-world prescribing guidelines, could prove a meaningful commercial differentiator for YORVIPATH, particularly with nephrology and endocrinology payers increasingly attentive to renal endpoints. Full data were to be made available on the Ascendis investor relations website.