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Bone and Mineral Metabolism

ORF16-07 - Palopegteriparatide Treatment in Adults with Hypoparathyroidism: Final Results of the Phase 3 PaTHway Trial

Saturday, June 13, 2026
2:45 PM - 3:00 PM CT
Location: Room W187



Introduction: Hypoparathyroidism is a rare endocrine disease caused by insufficient parathyroid hormone (PTH). Historically, conventional therapy with active vitamin D and calcium has aimed to correct associated hypocalcemia but does not address the underlying PTH insufficiency. Palopegteriparatide, a prodrug of PTH (1-34), has received regulatory approval in several countries for the treatment of hypoparathyroidism, based on the results from the phase 2 PaTH Forward and phase 3 PaTHway trials. Final long-term safety and efficacy results from PaTHway are presented here.

Methods: The phase 3 PaTHway trial included a 26-week, double-blind, placebo-controlled period followed by a 156-week open-label extension (OLE). Eighty-two adults with hypoparathyroidism were randomized and received ≥1 dose of study drug across 21 European and North American sites. All OLE participants received once-daily palopegteriparatide, with 73 participants (89%) completing the full OLE period.
Efficacy endpoints included independence from conventional therapy (≤600 mg/day of elemental calcium and no active vitamin D) and maintaining normocalcemia (8.3-10.6 mg/dL). Bone turnover markers, bone mineral density (BMD) T- and Z-scores, and renal function (estimated glomerular filtration rate (eGFR)) were assessed through Week 182. Patient-reported outcomes (PROs) addressing symptoms, physical functioning, and daily life were followed using validated hypoparathyroidism-specific measures through the end of the OLE. Safety assessments included treatment-emergent adverse events (TEAEs), serum chemistries, and 24-hour urine calcium.

Results: At Week 182, 96% of participants (70/73) were independent from therapeutic doses of calcium, none required active vitamin D, and 89% (65/73) maintained normal albumin-adjusted serum calcium with a mean (SD) value of 8.8 (0.5) mg/dL. Following an initial anticipated increase, mean bone turnover markers stabilized within the normal range. Elevated baseline mean BMD Z-scores trended towards age- and sex-matched norms and largely stabilized after 26 weeks, remaining above 0 through Week 182. Mean BMD Z-scores and T-scores followed consistent trends across sex and menopausal status. Early improvements in multiple PRO domains were maintained throughout the OLE. Mean eGFR increased from baseline and subsequently stabilized, with a mean increase of 11.0 mL/min/1.73m2 at Week 182. Elevated mean 24-hour urine calcium excretion levels declined and were normal through the OLE. Most TEAEs were mild or moderate; three participants discontinued treatment due to TEAEs unrelated to study drug.

Conclusions: Palopegteriparatide demonstrated durable safety and efficacy in adults with hypoparathyroidism, sustaining normocalcemia, enabling independence from conventional therapy, and improving multiple PRO domains for participants through Week 182.