Ascendis Pharma Reports Strong Phase 3 Durability Data for Yorvipath

Ascendis Pharma ($ASND) reported final long-term Phase 3 follow-up data for its hypoparathyroidism therapy TransCon PTH, showing sustained biochemical control and a sharp reduction in reliance on conventional supplements over nearly three and a half years—an outcome that could strengthen confidence in broader real-world uptake of the once-daily prodrug.

The Denmark-based drugmaker said the dataset comes from the Phase 3 ‘PaTHway’ trial in adults with hypoparathyroidism, consisting of a 26-week randomized, double-blind, placebo-controlled period followed by a 156-week open-label extension. In total, 82 patients were enrolled, and 73 participants—about 89%—completed 182 weeks of follow-up. The company presented the results on Friday in Copenhagen (June 13 ET).

At 182 weeks, 86% of patients met the study’s responder definition: maintaining normal serum calcium while taking no active vitamin D and limiting elemental calcium supplementation to 600 mg per day or less. Ascendis said 100% of participants remained off active vitamin D therapies such as calcitriol and alfacalcidol, while 96% no longer required ‘therapeutic-dose’ calcium supplementation—figures that underscore a durable shift away from the traditional management approach of high-dose calcium and active vitamin D.

Beyond serum calcium, Ascendis reported stability or normalization across key disease-related markers, including urinary calcium, phosphate levels, bone mineral density, kidney function, and patient-reported quality-of-life measures. Hypoparathyroidism is an endocrine disorder caused by insufficient parathyroid hormone (PTH), disrupting calcium and phosphate balance and potentially leading to neuromuscular irritability, renal complications, and cognitive impairment. Industry estimates cited by clinicians commonly suggest 70% to 80% of cases occur after neck surgery, including thyroid procedures.

Renal outcomes were a notable focus given the long-standing concern that conventional therapy can contribute to hypercalciuria and kidney complications. Ascendis said mean estimated glomerular filtration rate (eGFR) at week 182 was 80.2 mL/min/1.73㎡, up 11.0 mL/min/1.73㎡ from baseline. The company framed the improvement as meaningful against a typical backdrop of age-related eGFR decline. Twenty-four-hour urinary calcium reportedly normalized within 26 weeks and remained in the normal range through week 182.

Patient-reported outcomes also suggested persistent benefits. On the Hypoparathyroidism Patient Experience Scale (HPES) and the SF-36 health survey, Ascendis said participants showed rapid and ‘clinically meaningful’ improvements spanning physical symptoms, cognitive issues, everyday functioning, and overall well-being. Bone mineral density metrics, which initially showed elevated Z-scores, were corrected within 26 weeks and stayed at or above zero through the end of follow-up, according to the company.

“TransCon PTH has a unique mechanism that mimics the systemic actions of endogenous parathyroid hormone and alleviated physical and psychological burden in many patients,” said Aliya Khan of McMaster University’s Faculty of Health Sciences, citing improvements in fatigue, cognitive challenges, and physical limitation that can define the condition’s day-to-day impact.

On safety, Ascendis said most adverse events were mild to moderate, with no discontinuations attributed to the drug. The company also reported no cases of anti-PTH antibodies over the 182-week treatment period and said no new safety signals were identified.

Amy S. Shu, Ascendis’ chief medical officer, said the data indicate TransCon PTH can normalize key biochemical parameters and skeletal health regardless of underlying cause, while delivering measurable gains in kidney function and quality of life.

TransCon PTH is a once-daily PTH(1-34) prodrug designed to provide steady, physiologic-range active PTH exposure over 24 hours. The therapy has already been approved in the U.S. and the European Union for adults with hypoparathyroidism under the brand name ‘Yorvipath.’ With multi-year durability now documented in a controlled Phase 3 cohort, the company’s latest update is likely to reinforce the view that long-acting PTH replacement could meaningfully reduce dependence on supplement-heavy ‘standard-of-care’ regimens—an important consideration for long-term disease management and prescribing patterns.