Positive topline results were announced from a phase 3 trial evaluating the efficacy and safety of TransCon™ PTH in adults with hypoparathyroidism.

TransCon PTH is an investigational once-daily long-acting prodrug of parathyroid hormone (PTH[1-34]) designed to restore physiologic levels of PTH for 24 hours each day. The multicenter, randomized, double-blind, placebo-controlled, parallel group PaTHway trial (ClinicalTrials.gov Identifier: NCT04701203) included 82 adults with chronic hypoparathyroidism. Patients were randomly assigned 3:1 to receive TransCon PTH 18mcg subcutaneously once daily or placebo for 26 weeks. 

Findings demonstrated that 78.7% (n=48/61) of patients treated with TransCon PTH met the primary endpoint achieving serum calcium levels within normal range (8.3-10.6mg/dL) and independence from therapeutic levels of conventional therapy (active vitamin D and >600mg/day of calcium supplements) compared with 4.8% (n=1/21) of patients who received placebo (P <.0001).

Treatment with TransCon PTH was also associated with statistically significant improvements in physical and cognitive symptoms as measured by the Hypoparathyroidism Patient Experience Scales (HPES) Symptom-Physical domain score (P =.0038), HPES Symptom-Cognitive domain score (P =.0055), HPES Impact-Physical Functioning domain score (P =.0046), the HPES Impact-Daily Life domain score (P =.0061), and the SF-36v2 survey Physical Functioning subscale score (P =.0347).

At week 26, 95% of patients treated with TransCon PTH were able to discontinue conventional treatment with therapeutic levels of calcium supplements and active vitamin D. Moreover, patients treated with TransCon PTH demonstrated increased levels of bone turnover markers at week 26.

As for safety, TransCon PTH was well tolerated with no discontinuations related to the study drug. Treatment-emergent adverse events were reported in 82% of TransCon PTH-treated patients and 100% of placebo-treated patients.

Seventy-nine patients who completed the blinded period opted to continue in an open-label extension portion of the study for up to 3 years. The Company intends to submit a New Drug Application (NDA) to the Food and Drug Administration (FDA) in the third quarter of 2022.

“Conventional therapy with calcium supplements and active vitamin D is aimed at maintaining serum calcium in the normal range, with the hope of reducing short-term symptoms, and is not able to address the underlying disease,” said Jan Mikkelsen, Ascendis Pharma’s President and CEO. “This is the first phase 3 trial where more than three quarters of patients achieved control of their hypoparathyroidism, defined as normalization of serum calcium and independence from conventional therapy.”

Reference

Ascendis Pharma A/S announces phase 3 PaTHway trial of TransCon™ PTH in adults with hypoparathyroidism met primary and all key secondary endpoints. News release. Ascendis Pharma A/S. March 13, 2022. Accessed March 15, 2022. https://investors.ascendispharma.com/news-releases/news-release-details/ascendis-pharma-announces-phase-3-pathway-trial-transcontm-pth