TOPLINE:
Long-term treatment with TransCon parathyroid hormone (PTH), a replacement therapy for hypoparathyroidism, demonstrates sustained efficacy and safety in patients with hypoparathyroidism over 52 weeks, with 95% of participants able to discontinue conventional therapy.
METHODOLOGY:
- Conventional therapy for hypoparathyroidism (active vitamin D and elemental calcium) alleviates symptoms of hypocalcemia, but it does not improve insufficient PTH levels and is linked to long-term complications, such as nephrocalcinosis, nephrolithiasis, and renal dysfunction.
- This phase 3 (PaTHway) trial aimed to investigate the long-term efficacy, safety, and tolerability of TransCon PTH (palopegteriparatide) in adults with hypoparathyroidism.
- Overall, 82 patients with chronic hypoparathyroidism (mean age, 48.6 years; 78% women; 93% White) were randomly assigned to receive TransCon PTH or placebo, both coadministered with conventional therapy for 26 weeks.
- At the 26-week visit, patients who completed the blinded treatment (n = 79) were assigned to receive only TransCon PTH with conventional therapy in an ongoing 156-week open-label extension.
- For this analysis at week 52, the main efficacy endpoint was the proportion of patients (n = 78) with normal serum calcium levels (8.3-10.6 mg/dL) and independence from conventional therapy (active vitamin D and therapeutic doses of calcium); safety assessments included serum chemistries, 24-hour urine calcium excretion, and treatment-emergent adverse events.
TAKEAWAY:
- At week 52, the majority of the patients receiving TransCon PTH achieved normal serum calcium levels within the normal range (86%) and independence from conventional therapy (95%). None required active vitamin D.
- In secondary endpoints, patients receiving TransCon PTH showed sustained improvement in Hypoparathyroidism Patient Experience Scale scores, reflecting better symptom management, enhanced functioning, and overall well-being through week 52.
- At week 52, the mean 24-hour urine calcium excretion in patients first randomized to TransCon PTH was 185.1 mg/d, remaining well below the upper limit of normal (≤ 250 mg/d), while the placebo group mean fell to 223.1 mg/d during the open-label extension of TransCon PTH.
- TransCon PTH was well-tolerated, with most treatment-emergent adverse events being mild or moderate and none leading to treatment discontinuation.
IN PRACTICE:
“These results suggest that TransCon PTH may improve outcomes and advance the standard of care for adults living with hypoparathyroidism,” the authors wrote.
SOURCE:
The study was led by Bart L. Clarke, MD, Mayo Clinic, Rochester, Minnesota. It was published online in The Journal of Clinical Endocrinology & Metabolism.
LIMITATIONS:
The study’s limitations included the open-label design during the extension period, which may have introduced bias in patient-reported outcomes. Additionally, the study population was predominantly women and White, which may have limited the generalizability of the findings. Further research is needed to assess the long-term effects of TransCon PTH on renal complications. One patient died of fatal cardiac arrest deemed unrelated to the study drug.
DISCLOSURES:
The study was funded by Ascendis Pharma A/S. Seven authors declared being current or former employees of Ascendis Pharma. The other authors declared receiving grants, research funding, honoraria, serving as consultants, advisory board members, study investigators, and other ties with Ascendis Pharma and multiple other pharmaceutical companies.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.
