Three-year follow-up from Ascendis Pharma’s PaTH Forward (Phase 2) and PaTHway (Phase 3) trials in adults with chronic hypoparathyroidism shows sustained improvement in renal function, continued normalization of urine calcium handling, and continued safety and efficacy on daily palopegteriparatide (TransCon PTH). The company will present the dataset as a poster at ASN Kidney Week 2025.
The core development is not a new efficacy signal but long-duration outcomes in an already approved product. TransCon PTH, marketed as YORVIPATH in the United States and European Union, will now be backed by consolidated multi-year renal data from two pivotal programs. The poster aggregates three-year results focused on kidney health metrics that have outsized relevance in hypoparathyroidism, where chronic hypercalciuria, nephrolithiasis, and nephrocalcinosis have been persistent drawbacks of conventional calcium and active vitamin D therapy.
Strategically, anchoring the post-approval narrative on renal protection is a calculated lifecycle move. For an endocrine replacement therapy designed to restore physiologic PTH signaling, demonstrating organ-level benefits beyond serum calcium control strengthens differentiation versus supplementation-based regimens and any future PTH-pathway entrants. It also addresses the specific domain in which clinicians, guideline bodies, and payers have historically expressed concern: the long-term renal burden of standard care. Suppose the three-year data show stable or improved kidney function, along with normalized urinary calcium over time. In that case, the company gains leverage for health-economic arguments and potential labeling refinements tied to renal outcomes. More broadly, it signals an intention to reposition hypoparathyroidism management around disease modification and organ preservation rather than episodic electrolyte correction.
Operationally, the readout touches several stakeholders. Endocrine and nephrology practices may see more structured comanagement, with protocolized monitoring of 24-hour urine calcium and eGFR trajectories during and after transitions off high-dose supplements. Sites running extension cohorts will note the feasibility of long-term follow-up and the logistics of serial renal assessments, including potential imaging for calcifications. CROs and data vendors can expect continued demand for centralized lab workflows and adjudication of renal events across multi-year time horizons. For regulators, consistent, durable renal outcomes could open dialogues on endpoint selection and post-marketing commitments in this class. Payers and HTA bodies will push for quantification of eGFR slope, rates of hypercalciuria normalization, incidence of stones or nephrocalcinosis, and any signals of reduced ER visits or hospitalizations linked to calcium derangements.
What to watch next is specificity. The field will look for the actual magnitude of eGFR change or stabilization versus baseline, the proportion of patients maintaining normocalciuria off conventional supplementation, and longer-term safety trends typical of chronic hormone replacement. The absence of a long-term randomized comparator will remain a limitation; real-world registries and claims analyses could fill gaps if Ascendis stands up structured post-approval evidence programs. Access and adoption will still hinge on payer criteria, clinic capacity to support onboarding and monitoring, and patient adherence to daily administration. Competitive dynamics also bear monitoring as any next-wave PTH analogs or alternative mechanisms approach the clinic; renal endpoints will likely become the battleground. If the Kidney Week dataset delivers robust, quantitative kidney outcomes, expect pressure on practice guidelines to shift toward earlier PTH replacement in appropriate patients and a growing emphasis on renal preservation as a standard endpoint in future hypoparathyroidism trials.
Jon Napitupulu is Director of Media Relations at The Clinical Trial Vanguard. Jon, a computer data scientist, focuses on the latest clinical trial industry news and trends.
