Palopegteriparatide Treatment Improves Renal Function in Adults with Chronic Hypoparathyroidism: 1-Year Results from the Phase 3 PaTHway Trial

Abstract

Introduction: Individuals with chronic hypoparathyroidism managed with conventional therapy (active vitamin D and calcium) have an increased risk for renal dysfunction versus age- and sex-matched controls. Treatments that replace the physiologic effects of parathyroid hormone (PTH) while reducing the need for conventional therapy may help prevent a decline in renal function in this population. This post hoc analysis examined the impact of palopegteriparatide treatment on renal function in adults with chronic hypoparathyroidism.

Methods: PaTHway is a phase 3 trial of palopegteriparatide in adults with chronic hypoparathyroidism that included a randomized, double-blind, placebo-controlled 26-week period followed by an ongoing 156-week open-label extension (OLE) period. Changes in renal function over 52 weeks (26 weeks blinded + 26 weeks OLE) were assessed using estimated glomerular filtration rate (eGFR). A subgroup analysis was performed with participants stratified by baseline eGFR < 60 or ≥ 60 mL/min/1.73 m².

Results: At week 52, over 95% (78/82) of participants remained enrolled in the OLE and of those, 86% maintained normocalcemia and 95% achieved independence from conventional therapy (no active vitamin D and ≤ 600 mg/day of calcium), with none requiring active vitamin D. Treatment with palopegteriparatide over 52 weeks resulted in a mean (SD) increase in eGFR of 9.3 (11.7) mL/min/1.73 m² from baseline (P < 0.0001) and 43% of participants had an increase ≥ 10 mL/min/1.73 m². In participants with baseline eGFR < 60 mL/min/1.73 m², 52 weeks of treatment with palopegteriparatide resulted in a mean (SD) increase of 11.5 (11.3) mL/min/1.73 m² (P < 0.001). One case of nephrolithiasis was reported for a participant in the placebo group during blinded treatment; none were reported through week 52 with palopegteriparatide.

Conclusion: In this post hoc analysis of the PaTHway trial, palopegteriparatide treatment was associated with significantly improved eGFR at week 52 in addition to previously reported maintenance and normalization of serum and urine biochemistries. Further investigation of palopegteriparatide for the preservation of renal function in hypoparathyroidism is warranted.

Trial registration: ClinicalTrials.gov NCT04701203.

Keywords: Clinical trial; Glomerular filtration rate; Hypoparathyroidism; Kidney; Palopegteriparatide; Parathyroid hormone; Renal disease; TransCon PTH.

Fig. 1

Mean (SD) changes from baseline in eGFR through week 52 of the PaTHway trial for the overall population and by baseline eGFR subgroup (< 60 or ≥ 60 mL/min/1.73 m²). Participants randomized to palopegteriparatide at baseline (n = 61) are shown in dark blue, and participants randomized to placebo (n = 21) are shown in white during the blinded period and light blue starting at week 26 when palopegteriparatide treatment was initiated (shaded region). At baseline, 19 participants randomized to palopegteriparatide and 4 randomized to placebo had baseline eGFR < 60 mL/min/1.73 m². Abbreviations: eGFR, estimated glomerular filtration rate; SD, standard deviation

Fig. 2

Proportion of participants from the PaTHway trial with an increase ≥ 5 mL/min/1.73 m² and ≥ 10 mL/min/1.73 m² in eGFR from baseline to weeks 26 and 52. Participants randomized to palopegteriparatide at baseline (n = 61) are shown in dark blue, and participants randomized to placebo (n = 21) are shown in white during the blinded period and light blue starting at week 26 when palopegteriparatide treatment was initiated. Abbreviations: eGFR, estimated glomerular filtration rate