Efficacy and safety of palopegteriparatide treatment in adults with hypoparathyroidism: 3-year results from the phase 3 PaTHway trial

Abstract

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 evaluated the long-term efficacy and safety of palopegteriparatide in adults with chronic hypoparathyroidism through week 156 of PaTHway, a phase 3 trial with a 26-week randomized, double-blind, placebo-controlled period, followed by an open-label extension.

Results

At week 156, 89% (73/82) of participants remained in the trial; of those, 96% were independent from conventional therapy (no active vitamin D and ≤ 600 mg/day elemental calcium) and 88% had normal albumin-adjusted serum calcium (2.07–2.64 mmol/L) with a mean (SD) of (2.2 [0.2] mmol/L). Mean (SD) serum phosphate (1.1 [0.2] mmol/L) and calcium × phosphate product (2.5 [0.4] mmol²/L²) remained within normal ranges. Mean (SD) eGFR was 78.0 (14.5) mL/min/1.73 m², reflecting a mean (SD) increase of 8.8 (11.9) mL/min/1.73 m² from baseline (P < 0.0001); 59% and 43% of participants had an increase in eGFR of ≥ 5 mL/min/1.73 m² and ≥ 10 mL/min/1.73 m², respectively. Mean (SD) 24-hour urine calcium levels normalized with palopegteriparatide treatment, remaining below the upper limit of normal (≤ 250 mg/day) through week 156 (162.1 [117.8] mg/day). TEAEs were mostly grade 1 or 2, with no new safety signals identified.

Discussion

Through year 3 of the PaTHway trial, retention rate was high and palopegteriparatide demonstrated consistent longer-term safety and efficacy, which included the maintenance of serum and urine biochemistries within normal levels and sustained improvement in renal function.