Palopegteriparatide Treatment Improves Renal Function in Adults with Chronic Hypoparathyroidism: 1-Year Results from the Phase3 PaTHway Trial.

Abstract

Individuals with chronic hypoparathyroidism managed with conventional therapy (active vitaminD 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. PaTHway is a phase3 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 52weeks (26weeks blinded + 26weeks OLE) were assessed using estimated glomerular filtration rate (eGFR). A subgroup analysis was performed with participants stratified by baseline eGFR < 60 or ≥ 60mL/min/1.73m2. At week52, 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 vitaminD and ≤ 600mg/day of calcium), with none requiring active vitaminD. Treatment with palopegteriparatide over 52weeks resulted in a mean (SD) increase in eGFR of 9.3 (11.7)mL/min/1.73m2 from baseline (P < 0.0001) and 43% of participants had an increase ≥ 10mL/min/1.73m2. In participants with baseline eGFR < 60mL/min/1.73m2, 52weeks of treatment with palopegteriparatide resulted in a mean (SD) increase of 11.5 (11.3) mL/min/1.73m2 (P < 0.001). One case of nephrolithiasis was reported for a participant in the placebo group during blinded treatment; none were reported through week52 with palopegteriparatide. In this post hoc analysis of the PaTHway trial, palopegteriparatide treatment was associated with significantly improved eGFR at week52 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. ClinicalTrials.gov NCT04701203.