COPENHAGEN, Denmark — Ascendis Pharma A/S (Nasdaq: ASND) today announced new data demonstrating early, sustained, and clinically meaningful improvements in kidney function in adults with hypoparathyroidism treated with TransCon® PTH (palopegteriparatide) for up to 5 years in the Company’s Phase 2 PaTH Forward and Phase 3 PaTHway trials. Results from the pooled analysis were shared in a poster presented by nephrologist Elvira Gosmanova, M.D., Professor of Medicine at Albany Medical College, during Kidney Week 2026, the annual meeting of the American Society of Nephrology.
“These groundbreaking improvements in renal function underscore the unique ability of TransCon PTH to replicate the systemic and balanced actions of endogenous PTH across multiple target organ systems,” said Aimee Shu, Executive Vice President and Chief Medical Officer at Ascendis Pharma. “We are pleased to showcase these benefits of TransCon PTH showing simultaneous improvements across key measures that include maintained normal serum calcium, decreased urine calcium, and sustained increases in eGFR, while enabling independence from conventional therapy.”
Historically, management of hypoparathyroidism with conventional therapy consisting of active vitamin D and calcium with the aim of raising serum calcium to the lower half or just below the reference range to alleviate symptoms of hypocalcemia and avoid hypercalciuria, but did not address the missing parathyroid hormone (PTH).i Today, in contrast, it is possible to provide or restore the full range of effects of PTH that are missing in hypoparathyroidism with TransCon PTH, which provides active PTH within the physiological range for 24 hours/day. The active PTH released from TransCon PTH includes the amino acid sequence identical to the region of endogenous PTH required for receptor activation and enables simultaneous improvements across multiple key clinical and quality-of-life measures.ii,iii
Data Highlights
- Increases in mean estimated glomerular filtration rate (eGFR) from baseline were statistically significant across patients from Week 26 of treatment through trial completion (p< 0.0001).
- Mean improvement in eGFR for all patients from baseline to Week 26 was 7.2 mL/min/1.73 m2 and to Week 52 was 9.6 mL/min/1.73 m2.
- By Week 52, clinically meaningful improvements in eGFR (≥ 5 mL/min/1.73 m2) iv,v were observed in 68.9% of patients, and 49.6% of patients achieved an increase in eGFR of >10 mL/min /1.73 m2; eGFR remained stable through the end of the trials.
- From Week 52 to Week 266, the mean eGFR slope was 0.28 mL/min/1.73 m2/year, indicating clinically meaningful early improvements in eGFR sustained through up to 5 years, in contrast to the expected typical age-related decline in eGFR in adults.vi
- Patients with baseline eGFR values < 60 mL/min/1.73 m2 had a numerically greater increase in mean eGFR than those with a baseline eGFR ≥ 60 mL/min/1.73 m2.
- 24-hour urine calcium excretion normalized by Week 26 from mean 396 mg/day at baseline to mean 206 mg/day at Week 26 and further decreased from Week 26 to mean 170 mg/day at Week 52, with improvements sustained through the end of the trials.
- 98% of patients achieved independence from active vitamin D, defined as taking no calcitriol or alfacalcidol, at final trial visit.
- 95% of patients achieved independence from therapeutic doses of calcium, defined as taking <600 mg/day of calcium, at final trial visit.
- Mean serum calcium increased within the normal range to 8.9 mg/dL, with 88% of patients having normal albumin-adjusted serum calcium levels at final trial visit.
- In both trials, TransCon PTH was generally well tolerated, with no new safety signals identified. Most treatment-emergent adverse events (TEAEs) were mild to moderate (Grade 1 or 2).
The PaTH Forward and PaTHway trials included a combined total of 141 adults with hypoparathyroidism. The pooled kidney data analysis covers the 139 patients who received at least one dose of TransCon PTH. Of these, 129 completed the final trial visit. The PaTH Forward and PaTHway trials comprised randomized, double-blind, placebo-controlled periods through Weeks 4 and 26 and open-label extension periods through Weeks 266 and 182, respectively. An eGFR ≥30 mL/min/1.73 m2 was required for trial eligibility. Mean (SD) baseline eGFR for the pooled analysis was 69 (17) mL/min/1.73 m2. The pooled data were analyzed post-hoc and included evaluation of the impact of TransCon PTH on renal function, as assessed by, change from baseline in eGFR and proportion of patients with an increase in eGFR ≥5 mL/min/1.73 m2, as well as 24-hour urinary calcium.
About TransCon PTH
TransCon PTH is a prodrug of PTH (1-34), administered once daily, designed to provide active PTH within the physiological range for 24 hours/day, approved as YORVIPATH® in the United States, European Union, European Economic Area, and other jurisdictions as a treatment for adults with hypoparathyroidism.
About Hypoparathyroidism
Hypoparathyroidism is an endocrine disease caused by insufficient levels of parathyroid hormone (PTH), the primary regulator of calcium and phosphate balance in the body, acting directly on bone and kidney and indirectly on the intestine. Individuals with hypoparathyroidism may experience a range of severe and potentially life-threatening short-term and long-term complications, including neuromuscular irritability, renal complications, extra-skeletal calcifications, and cognitive impairment. Post-surgical hypoparathyroidism accounts for the majority of cases (70-80%), while other etiologies include autoimmune, idiopathic, and genetic causes, including ADH1.
About Ascendis Pharma A/S
Ascendis Pharma is a global biopharmaceutical company focused on applying our innovative TransCon technology platform to make a meaningful difference for patients. Guided by our core values of Patients, Science, and Passion, and following our algorithm for product innovation, we apply TransCon to develop new therapies that demonstrate best-in-class potential to address unmet medical needs. Ascendis is headquartered in Copenhagen, Denmark, and has additional facilities in Europe and the United States. Please visit ascendispharma.com to learn more.
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References
i Khan AA, Bilezikian JP, Brandi ML, et al. J Bone Miner Res. 2022; 37(12):2568-2585.
ii Holten-Andersen L, Pihl S, Rasmussen CE, et al. J Bone Miner Res. Nov 2019;34(11):2075-2086. doi:10.1002/jbmr.3824.
iii Karpf DB, Pihl S, Mourya S, et al. J Bone Miner Res. Aug 2020;35(8):1430-1440. doi:10.1002/jbmr.4016.
iv Mayne TJ, et al. Clin Transplant. 2021;35(7):e14326.
v Ku E, et al. J Am Soc Nephrol. 2016;27(7):2196-204.
vi Guppy M et al. BMJ Open. 2024;14(11):e089783. doi:10.1136/bmjopen-2024-089783.