SUN-770 - Palopegteriparatide Enhances Work Functioning and Productivity in Employed Adults with Chronic Hypoparathyroidism: 156-Week Results from the Pathway Trial

Introduction: Hypoparathyroidism is a rare endocrine disease caused by insufficient levels of parathyroid hormone (PTH) and is associated with reduced quality of life and a high comorbidity burden. Conventional therapy for hypoparathyroidism (active vitamin D and calcium) aims to alleviate hypocalcemia but does not address insufficient PTH. 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, Japan, and several other countries. This analysis assessed job performance and productivity among employed adults with chronic hypoparathyroidism treated with palopegteriparatide through Week 156 of the PaTHway trial.

Methods: The phase 3 PaTHway trial included a 26-week randomized, double-blind, placebo-controlled period (DBP) followed by an open-label extension (OLE) period. The WLQ-25, a self-administered instrument, was administered to employed participants to measure the impact of hypoparathyroidism and palopegteriparatide on Time Management, Physical Demands, Mental–Interpersonal Demands, and Output Demands over the previous two weeks. Scores ranged from 0–100, with higher scores indicating greater limitations. At-work productivity loss was also calculated. Changes from baseline were assessed for the palopegteriparatide and placebo groups during the DBP and for all participants receiving palopegteriparatide during the OLE.

Results: At baseline (n=56), both groups had comparable mean scores across all domains except Physical Demands, indicating an impact on job performance. By Week 26, participants treated with palopegteriparatide showed substantial improvements in mean work limitation scores compared to their baseline scores in all domains: Time Management (improved from 32.0 to 11.3), Physical Demands (improved from 20.4 to 9.0), Mental–Interpersonal (improved from 27.8 to 8.9), and Output Demands (improved from 31.2 to 9.9). These improvements were greater than those in the placebo group for all domains, where no improvements were observed during the DBP. Improvements observed with palopegteriparatide treatment were maintained through Week 156, including for participants who crossed over from placebo to palopegteriparatide in the OLE. At-work productivity loss improved by 65% for participants in the palopegteriparatide treatment group during the DBP (lowering from 7.7% to 2.7%) and remained low (2.23%) through Week 156.

Conclusions: Palopegteriparatide treatment led to early improvements in work functioning and productivity in employed adults with chronic hypoparathyroidism. Benefits were observed across all WLQ-25 domains and sustained over three years. These findings support the long-term functional and potential economic value of palopegteriparatide treatment for adults with chronic hypoparathyroidism.

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