Kerry Willis
Chief Scientific Officer National Kidney Foundation
Seminars
As novel therapies emerge across the spectrum of CKD and rare glomerular diseases, developers face complex questions about regulatory expectations outside of IgA nephropathy. This interactive workshop will explore how agencies such as the FDA and EMA are evaluating surrogate endpoints, comparator requirements, and patient-centered outcomes in under-studied disease areas. With input from regulators, pharma, and trialists, the session will examine the evolving role of biomarkers, patient-reported outcomes, and real-world evidence in shaping accelerated approval pathways. Participants will gain a clear understanding of how to strategically design trials, minimize placebo burden, and align early with regulators to bring transformative therapies to patients faster.
Key Objectives:
- Evaluating acceptance of surrogate and composite endpoints (e.g., proteinuria reduction, MEG90, imaging biomarkers) in rare kidney diseases
- Understanding regulatory views on trial design in landscapes with multiple therapeutic classes and existing standards of care
- Incorporating patient-reported outcomes and real-world evidence into approval pathways to reduce placebo burden and enhance relevance
- Learning from recent case studies (e.g., Apellis in C3G, Filspari) to navigate accelerated approvals and companion diagnostic considerations
- The new Kidney HCE framework combines GFR slope, various thresholds of GFR decline (e.g. ≥ 40%, 50%, 57%), ESKD, and mortality in a hierarchical ordering to improve trial sensitivity and clinical relevance
- Regulatory bodies (NKF/FDA/EMA) are increasingly recognizing eGFR slope + albuminuria + clinical endpoints as valid surrogates, but the choice of thresholds, population, and follow-up duration remain critical
- Key methodological challenges include deciding component priorities, handling multiplicity, ensuring interpretability for patients & payers, and choosing proper statistical methods (win-odds, hierarchical ranking) to avoid bias
- Use-cases in broad CKD and rare subpopulations (e.g. IgA nephropathy, PKD) differ: design of HCEs must adapt thresholds, endpoints composition, and regulatory acceptability depending on disease, severity, and existing therapies
