Qualitative Analysis and Comparison of Externally Led Patient-Focused Drug Development Concepts for Autosomal...

Autosomal recessive polycystic kidney disease (ARPKD) is a rare, inherited condition associated with pathogenic variants in the PKHD1 gene, leading to fibrocystin dysfunction. ARPKD carries significant morbidity, involving progressive kidney dysfunction that often necessitates transplantation or dialysis. Liver complications commonly accompany renal manifestations and contribute to marked clinical heterogeneity and challenging disease management. Current therapies focus on alleviating complications rather than halting or reversing disease progression. Against this backdrop, patient-focused drug development (PFDD) has emerged to incorporate patients' perspectives and priorities into medical product development and care. On August 29, 2023, an externally led PFDD meeting brought together ARPKD patients, caregivers, clinicians, researchers, industry stakeholders, and regulators. These discussions highlighted the urgent need for treatments that address both renal and hepatic complications, improve quality of life, and mitigate disease burdens. This initiative also provided an opportunity to compare ARPKD patient-identified priorities with outcomes from previous Standard Outcome in Nephrology Group efforts. Commonalities included the emphasis on quality of life and functional measures. ARPKD- externally led PFDD-specific considerations were early-onset disease and combined kidney-liver pathology. Incorporating these insights into clinical trial designs and regulatory frameworks holds promise for more meaningful outcome measures and the advancement of ARPKD novel therapies.