Five-Year Phase 2 Data Show TransCon PTH Sustains Multi-Organ Benefits in Hypoparathyroidism
核心洞察
Ascendis Pharma announced 5-year Phase 2 PaTH Forward Trial data showing TransCon PTH (palopegteriparatide) sustained efficacy and safety in adults with hypoparathyroidism (搜索).
82% of patients met the multi-component endpoint of normal serum calcium, no active vitamin D, and less than 600 mg/day calcium, with 95% completing the full five-year trial.
Significant improvements in kidney function were maintained, with a mean eGFR increase of 9.4 mL/min/1.73 m² from baseline, contrasting with expected age-related decline.
COPENHAGEN, Denmark — Ascendis Pharma A/S (Nasdaq: ASND) announced on June 11, 2026 that five-year data from its Phase 2 PaTH Forward Trial demonstrate sustained efficacy and safety of TransCon PTH (palopegteriparatide) in adults with hypoparathyroidism (搜索), with the therapy replicating the systemic actions of endogenous parathyroid hormone across multiple organ systems.
The results, presented by Andrea Palermo, M.D., Ph.D., an endocrinologist at Campus Bio-Medico University in Rome, during the European Congress of Endocrinology (ECE) 2026, showed that long-term treatment with TransCon PTH delivered a balanced, beneficial impact on the main target organ systems — kidney, small intestine, central nervous system, and bone — as demonstrated by normalized and stable urine calcium, serum calcium, quality of life, and bone mineral density.
"Moving from symptom management to addressing the underlying hormone deficiency requires normalization of PTH biology to mitigate the multi-organ impacts of hypoparathyroidism (搜索). TransCon PTH has achieved this, meeting the high bar for the treatment of chronic hypoparathyroidism," said Dr. Palermo. "These data demonstrate the consistent, long-term benefits of this therapy and reinforce its potential as the emerging standard of care for the treatment of hypoparathyroidism."
Multi-Component Endpoint and Biochemical Control
At Week 266, 82% of patients met the multi-component responder endpoint, defined as serum calcium in the normal range, taking no active vitamin D, and taking less than 600 mg/day of calcium. Normal albumin-adjusted serum calcium levels were achieved by 88% of patients, with a mean value of 9.0 mg/dL.
Independence from conventional therapy was nearly universal: 96% of patients achieved independence from active vitamin D (defined as not taking calcitriol or alfacalcidol), and 95% achieved independence from therapeutic doses of calcium (defined as taking less than 600 mg/day).
Renal Function Improvements
Significant improvements in kidney function were maintained throughout the five-year treatment period. At Week 266, the mean estimated glomerular filtration rate (eGFR) was 78.0 (SE: 3.0) mL/min/1.73 m², reflecting a mean increase of 9.4 (SE: 1.9) mL/min/1.73 m² from baseline. Improvements were evident as early as Week 4, increased through Week 58, and were sustained over five years of treatment, in contrast to the expected normal age-related decline in eGFR in adults.
Mean 24-hour urine calcium decreased substantially, normalized within 26 weeks, and remained normal through Week 266.
Quality of Life and Bone Health
Patient-reported outcomes, measured by the Hypoparathyroidism (搜索) Patient Experience Scales (HPES), showed improvements in symptoms and health-related quality of life across all domains. Hypoparathyroidism-related physical and cognitive symptoms and impacts on physical functioning and daily life improved rapidly with TransCon PTH treatment and were maintained through Week 266.
As measured by the SF-36, all mean health-related quality of life subscale and component summary scores rapidly normalized with TransCon PTH treatment and remained in the normative range through Week 266.
Mean bone mineral density (BMD) Z-scores, matched for age and sex, corrected from high baseline levels through Week 26 and remained above 0 through Week 266.
Safety Profile
TransCon PTH was generally well-tolerated over the five-year treatment period, with no new safety signals identified. Treatment-emergent adverse events were mostly mild or moderate, and no discontinuations were related to the study drug. One patient developed transient, low-titer and non-neutralizing anti-PTH antibodies, with no impact on safety or efficacy. Over five years of treatment, no other patients developed anti-PTH antibodies.
"Across clinical trials and etiologies, TransCon PTH has shown a unique ability to replicate the actions of endogenous PTH, normalizing biochemistries and skeletal health and significantly improving kidney function and quality of life," said Aimee Shu, M.D., Executive Vice President and Chief Medical Officer at Ascendis Pharma. "We are pleased to see TransCon PTH working as designed to transform treatment for patients living with this often-debilitating chronic disease."
Trial Design and Patient Population
The PaTH Forward Trial enrolled 59 adults with hypoparathyroidism (搜索), of whom 80% had post-surgical disease and 20% had non-surgical etiologies. The trial included a 4-week randomized, double-blind, placebo-controlled period followed by a 262-week open-label extension period. Notably, 56 of the original 59 patients (95%) completed the full five-year trial.
Endpoints included independence from conventional therapy (defined as less than 600 mg/day of calcium and no active vitamin D), maintenance of normocalcemia (8.3 to 10.6 mg/dL), renal function assessed by eGFR, bone mineral density measured by DXA scan, hypoparathyroidism (搜索)-related symptoms and functional impacts measured by HPES, and health-related quality of life measured by the SF-36 version 2.
TransCon PTH is a prodrug of PTH (1-34), administered once daily, designed to provide stable levels of active PTH within the physiological range for 24 hours per day. It is approved as YORVIPATH in the United States, European Union, European Economic Area, and certain other jurisdictions for the treatment of adults with hypoparathyroidism (搜索).
Disease Background
Hypoparathyroidism (搜索) is an endocrine disease caused by insufficient levels of parathyroid hormone, the primary regulator of calcium and phosphate balance in the body, acting directly on bone and kidney and indirectly on the intestine. Individuals with the condition 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.