Long-term efficacy and safety of palopegteriparatide treatment in adults with chronic hypoparathyroidism: 4-year results from the phase 2 PaTH forward trial

Introduction

Palopegteriparatide is a prodrug of PTH (1-34), administered once daily, designed to provide active PTH within the physiological range for 24 hours/day. It is approved in the US, EU, and several other countries. This analysis investigated the efficacy and safety of palopegteriparatide in adults with chronic hypoparathyroidism through week 214 of PaTH Forward, a phase 2 trial with a 4-week randomized, double-blind, placebo-controlled period, followed by open-label extension through week 266.

Observations

At week 214, 95% (56/59) of participants remained in the trial; of those, 93% were independent from conventional therapy (no active vitamin D and ≤ 600 mg/day elemental calcium) and 98% had normocalcemia (2.07–2.64 mmol/L). Mean bone turnover markers C-terminal telopeptide of type 1 collagen (CTx) and procollagen type 1 N-terminal propeptide (P1NP) increased from low end of normal at baseline, peaked by week 26, and declined thereafter, remaining stable above baseline. Elevated baseline mean BMD Z-scores trended towards age- and sex-matched norms at lumbar spine, femoral neck, and total hip, largely stabilized after week 26 and remained above zero. At week 214, mean (SD) eGFR was 86.0 (21.7) mL/min/1.73 m², reflecting a mean (SD) increase of 7.6 (13.7) mL/min/1.73 m² from baseline. Mean (SD) 24-hour urine calcium levels normalized with palopegteriparatide and were maintained (≤ 6.2 mmol/day). TEAEs were mostly mild/moderate; no new safety signals were identified.

Discussion

These results demonstrate sustained efficacy and safety of palopegteriparatide in adults with chronic hypoparathyroidism through week 214 of PaTH Forward, suggesting continued benefits in skeletal dynamics and renal function.