The PARASOL APOL1 and MN kickoff meeting in Minneapolis on October 9, 2025 convened nephrology experts, clinical trialists, and regulatory representatives to address the validation and application of surrogate endpoints in rare kidney diseases. Building on the success achieved in the original PARASOL-FSGS project, the discussion focused on the scientific and regulatory rigor required for surrogate endpoints such as proteinuria, anti-PLA2R antibodies, and eGFR slope.
Key points included:
- Regulatory representatives underscored the necessity for robust scientific evidence and biological plausibility in surrogate endpoint selection, with an emphasis on quantitative relationships and applicability across heterogeneous disease populations.
- Presenters highlighted the challenges of conducting trials in rare diseases with small, dispersed cohorts, and the importance of global data sharing to enhance statistical power and endpoint validation.
- The group debated the utility of proteinuria and PLA2R as surrogate endpoints, considering disease heterogeneity (e.g., FSGS, C3 glomerulopathy, APOL1-associated nephropathies) and genotype-specific modifiers.
- Discussions addressed the need for tailored trial designs that account for diverse patient populations, and the implications for regulatory approval pathways.
- Patient perspectives reinforced the clinical relevance of early diagnosis and effective intervention, as well as the importance of transparent communication regarding trial participation and outcomes.
This meeting set out a collaborative framework for advancing surrogate endpoint science and optimizing clinical trial methodologies in rare kidney diseases. On Friday, October 10, the discussion will continue in more detail for each project as the groups take inventory of potential datasets and begin designing analysis plans.
The PARASOL team is eager to collaborate with additional registries and stakeholders; anyone with interest in participating should contact parasol@is-gd.org.
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