Kidney Compass: Future of PARASOL and FSGS Management

Welcome to Kidney Compass: Navigating Clinical Trials!

In the fourth and final installment of our episode on the PARASOL Initiative and focal segmental glomerulosclerosis, special guests Laura Mariani, MD, MS, and Daniel Gale, PhD, MB BChir, discuss the next steps for the project and its potential to revolutionize drug development in FSGS. Hosts Brendon Neuen, MBBS, PhD, and Shikha Wadhwani, MD, MS, ask Mariani and Gale to explore how the initiative's findings provide a critical pathway for validating proteinuria as a surrogate endpoint in trials.

Gale underscores the importance of recognizing that proteinuria reduction—even without full remission—can serve as a meaningful measure for drug approval. However, he stresses that the drug's mechanism must directly address the underlying podocyte dysfunction central to FSGS pathology. He notes this flexibility could accelerate therapeutic development across various etiologies of FSGS, including genetic, immunologic, and injury-related forms.

Mariani reflects on the significant unmet need in FSGS, emphasizing that even modest reductions in proteinuria can delay dialysis or kidney transplantation—life-changing outcomes for patients. She calls for trial designs that include specimen banking to advance biomarker discovery and refine surrogate endpoints, further enhancing the precision and feasibility of future studies.

Looking ahead, the PARASOL Initiative will focus on publishing its groundbreaking findings and addressing outstanding questions about trial design. Both guests highlight the collaborative nature of this project as a model for tackling similar challenges in other rare kidney diseases. Dr. Gale notes that the Parasol community is a powerful asset for nephrology, offering infrastructure and partnerships to drive research forward in other conditions with limited treatment options.

Kidney Compass: The PARASOL Initiative

Part 1: Introductions

Part 2: PARASOL Background and FSGS Landscape

Part 3: PARASOL Findings and Implications for FSGS

Part 4: Future of PARASOL, FSGS Management (Current Segment)

Relevant disclosures for Neuen include AstraZeneca, Bayer, Boehringer and Ingelheim, Janssen, and others. Relevant disclosures for Wadhwani include the National Institute of Diabetes and Digestive and Kidney Diseases, GSK, Calliditas and Travere Therapeutics. Relevant disclosures for Mariani include Travere Therapeutics, Boehringer Ingelheim, Reliant Glycosciences, Takeda Pharmaceuticals, HI-Bio, and Calliditas Therapeutics. Relevant disclosures for Gale include Novartis, Alexion, Calliditas, Britannia, Vifor, Judo Bio, Adnovate, Sanofi, Anlylam, Boehringer Ingelheim, and Bayer.