52-Week Data from PaTHway Trial Further Supports TransCon PTH in Hypoparathyroidism

Bart L. Clarke, MD
Credit: Mayo Clinic

An analysis of data from the open-label extension of the phase 3 PaTHway trial suggests 95% of patients with hypoparathyroidism using TransCon PTH achieved independence from conventional therapy at 52 weeks, with safety and tolerability similar to initial 26-week results from the trial.¹

Results of the study, which were presented at the Endocrine Society 2023 annual meeting, come less than 2 months after Ascendis Pharma announced the receipt of a Complete Response Letter for TransCon PTH on May 1, 2023. In their announcement, Ascendis Pharma noted the FDA did not express concern about the clinical data submitted as part of the New Drug Application package and the company would be requesting a meeting with the agency to determine the best path forward.²

“We are very pleased to see sustained improvements in clinical outcomes in this trial, including symptom and health-related quality of life measures, consistent with those reported earlier for the initial 26-week blinded portion,” said Jan Mikkelsen, President and chief executive officer of Ascendis Pharma.³ “These clinical and patient-reported data, and the retention of 145 patients in our ongoing clinical trials, reinforces our confidence that TransCon PTH has the potential, if approved, to benefit adults with hypoparathyroidism regardless of disease etiology.”

The regulatory portion of the journey to a potential FDA approval for Ascendis Pharma’s long-acting prodrug for parathyroid hormone has dates back more than half a decade, with the agent granted an Orphan Drug Designation in June 2018.⁴ The May 2023 CRL from the FDA followed an April 3, 2023 announcement from the company disclosing a notification from the FDA regarding deficiencies in the NDA for palopegteriparatide in hypoparathyroidism precluding the agency from holding further discussions about labeling and post-marketing requirements/commitment.²

The application for TransCon PTH is based on data from the phase 3 PaTHway trial. A double-blind, placebo-controlled trial of 82 dosed adults with chronic hypoparathyroidism randomized in a 3:1 ratio to TransCon PTH or placebo therapy. The trial had a primary composite endpoint of serum calcium levels in the normal range and independence from conventional therapy with no increase in prescribed study drug within the 4 weeks prior to the week 26 visit.²

For the purpose of analysis, normal serum calcium levels were defined as 8.3–10.6 mg/dL and independence from conventional therapy was defined as independence from active vitamin D supplementation and independence from therapeutic doses of calcium supplements. The trial was designed with a 26-week blinded period and a 156-week open-label extension period. Analysis of the data from the 26-week blinded treatment period suggested 78.7% of patients in the TransCon PTH group achieved the primary endpoint compared to just 4.8% of the control group (P < .001).²

At ENDO 2023, 52-week data from the open-label extension period, which was presented by PaTHway investigator Bart L. Clarke, MD, of the Mayo Clinic, provided further insight into the effects of TransCon PTH. Among the 82 participants who received treatment during the trial, 79 completed the blinded treatment and entered the open-label extension period. Of these, 78 participants, including 59 initially randomized to TransCon PTH, completed week 52.¹

Upon analysis, results suggested 74 of the 78 participants achieved independence from conventional therapy at week 52 and none required active vitamin D supplementation. Investigators highlighted 81% of participants treated with TransCon PTH achieved both normal serum calcium and independence from conventional therapy, with further analysis indicating mean albumin-adjusted serum calcium levels were maintained within the normal range through week 52.¹

Additionally, investigators called attention to 52-week results suggesting sustained improvements in patient-reported scores pertaining to disease-related physical and cognitive symptoms starting at the first scheduled follow-up after randomization or switching from placebo through Week 52. When assessing bone mineral density Z-scores at week 52, results revealed a tend toward age- and sex-matched norms with 52 weeks of TransCon PTH treatment. Investigators also pointed out use of TransCon PTH was associated with normalized 24-hour urine calcium through week 52, regardless of initial randomization.¹

References:

1. Clarke B, Khan AA, Rubin MR, et al. Long-Term Efficacy and Safety of TransCon™PTH in Adults with Hypoparathyroidism: 52-Week Results From the Open-Label Extension of the Phase 3 PaTHway Trial. Paper presented at: the Endocrine Society annual meeting. June 15 – 18, 2023.
2. Campbell P. FDA issues complete response letter for transcon PTH in hypoparathyroidism. HCP Live. May 1, 2023. Accessed June 18, 2023. https://www.hcplive.com/view/fda-issues-complete-response-letter-transcon-pth-in-hypoparathyroidism.
3. One-year data from phase 3 trial of TransconTM pth in adults with hypoparathyroidism presented at endo 2023: Ascendis Pharma. One-Year Data from Phase 3 Trial of TransConTM PTH in Adults with Hypoparathyroidism Presented at ENDO 2023 | Ascendis Pharma. June 17, 2023. Accessed June 18, 2023. https://investors.ascendispharma.com/news-releases/news-release-details/one-year-data-phase-3-trial-transcontm-pth-adults.
4. Rosa K. FDA grants orphan drug designation to treatment for rare endocrine disorder. HCP Live. June 7, 2018. Accessed June 18, 2023. https://www.hcplive.com/view/fda-grants-orphan-drug-designation-to-treatment-for-rare-endocrine-disorder.