Phase III PaTHway trial of TransCon PTH in adults with hypoparathyroidism met primary and all key secondary endpoints.- Ascendis A/S

The primary endpoint – defined as serum calcium levels in the normal range (8.3–10.6 mg/dL) and independence from conventional therapy (active vitamin D and >600 mg/day of calcium supplements) with no increase in prescribed study drug within the 4 weeks prior to the Week 26 visit – was achieved by 78.7% of TransCon PTH-treated patients (48 of 61), compared to 4.8% for patients (1 of 21) in control group (p-value <0.0001).></0.0001).>

Highlights of the Phase III PaTHway Trial Top-Line Data: The PaTHway Trial is a Phase III double-blind, placebo-controlled trial of 82 dosed adults with chronic hypoparathyroidism randomized 3:1 (TransCon PTH:placebo). Primary Composite Endpoint : 78.7% of TransCon PTH-treated patients (48 of 61) achieved serum calcium levels in the normal range (8.3–10.6 mg/dL) and independence from therapeutic levels of conventional therapy, compared to 4.8% for patients (1 of 21) in control group (p-value = <0.0001).> Key Pre-Specified Secondary Endpoints : i.Statistically significant decrease in patient-reported, disease-specific physical and cognitive symptoms compared to patients in control group, as shown on Hypoparathyroidism Patient Experience Scales (HPES) Symptom-Physical domain scores (p-value = 0.0038) and HPES Symptom-Cognitive domain scores(p-value = 0.0055). ii. Statistically significant reduction in patient-reported disease impact compared to patients in control group, as shown on HPES Impact-Physical Functioning domain scores (p-value = 0.0046) and HPES Impact-Daily Life domain scores (p-value = 0.0061).iii. Statistically significant improvements in patient-reported physical functioning compared to patients in control group, as shown on the SF-36v2 survey Physical Functioning subscale (p-value = 0.0347).</0.0001).>

Selected other analyses : i.At Week 26, 95% of TransCon PTH-treated patients were able to discontinue conventional treatments with therapeutic levels of calcium supplements and active vitamin D. ii.PaTHway patients had low levels of bone turnover at baseline. TransCon PTH-treated patients demonstrated increased levels of bone turnover markers at Week 26.

Safety summary: TransCon PTH was generally well tolerated, with no discontinuations related to study drug. Three patients discontinued during the treatment period – 2 from the placebo arm and 1 from the TransCon PTH arm. 82% of TransCon PTH patients and 100% of patients in control group reported treatment-emergent adverse events (TEAEs), the majority of which were Grade 1, 2 in severity. One serious related TEAE in the TransCon PTH arm was reported due to a dosing error. One death in the TransCon PTH arm was assessed as unrelated to study drug. TransCon PTH-treated patients showed a mean decrease in 24-hour urine calcium excretion into the normal range, from 390 mg/24 hours down to 220 mg/24 hours. Despite a higher mean serum calcium at Week 26, there was a significantly greater decrease in mean 24-hour urine calcium for TransCon PTH-treated patients compared to patients in control group.

Following an initial blinded study period of 26 weeks, for which top-line data are reported here, all 79 patients completing the blinded period opted to receive treatment with TransCon PTH in the ongoing open-label extension portion of the study for up to 3 years (156 weeks). As of today, all 79 patients continue in the open label extension portion of the PaTHway Trial.

Ascendis plans to submit a New Drug Application (NDA) to the for TransCon PTH for adults with hypoparathyroidism during the third quarter of 2022 and a Marketing Authorisation Application (MAA) to the European Medicines Agency during the fourth quarter of 2022. Top-line results for the Phase III PaTHway Japan Trial are expected in the third quarter of 2022. In addition, Ascendis plans to initiate a clinical trial of TransCon PTH in pediatric hypoparathyroidism during the fourth quarter of 2022.