Kidney Compass: PARASOL Background and FSGS Landscape

Welcome to Kidney Compass: Navigating Clinical Trials!

In the second installment of our 4-part episode of Kidney Compass, Shikha Wadhwani, MD, MS, and Brendon Neuen, MBBS, PhD, dive into the groundbreaking work of the RADAR Registry and the PARASOL Initiative, with special guests Daniel Gale, PhD, MB BChir, and Laura Mariani, MD, MS.

RaDaR Registry: A Beacon for Real-World Data

Gale shares insights from the UK-based RaDaR Registry, a vast repository of real-world data from over 35,000 patients with rare kidney diseases. By capturing longitudinal data—spanning decades in some cases—RaDaR has revealed critical patterns in disease progression and the clinical parameters that predict long-term outcomes.

Beyond this, RaDaR has evidenced how partnerships with the UK Kidney Association and numerous investigators can build a community-driven framework for research.

PARASOL Initiative: Tackling FSGS Challenges

Next, Mariani highlights the unique obstacles in studying FSGS, from its biological heterogeneity to the difficulty of designing trials with meaningful endpoints. Unlike diseases like IgA nephropathy, which have benefited from regulatory pathways and increased drug development, FSGS remains a high-hurdle disease.

PARASOL aims to address these challenges b defining robust surrogate endpoints (e.g., proteinuria and GFR slope) to replace long-term kidney failure outcomes in trials and aggregating data from global cohorts, including Cure GN, RADAR, and others, to provide the statistical power necessary for meaningful analyses.

Mariani emphasizes the collaborative spirit behind PARASOL, crediting patient advocacy groups and international nephrologists for their willingness to contribute data and expertise. She notes that the initiative’s success is rooted in a shared mission to create a regulatory pathway for FSGS therapies, enabling innovation and hope for patients.

A Regulatory Partner: The FDA’s Role

According to Mariani and Gale, the US FDA’s involvement in PARASOL has been instrumental, guiding data analysis and evidence standards. The duo describe a 2-way learning process:

• Nephrologists educate FDA teams on the nuances of rare kidney diseases.
• FDA biostatisticians help researchers align their analyses with regulatory expectations, ensuring that findings can support drug approvals.

For ease of viewing, we've divided this episode, which contains more than an hour of insights into the PARASOL Initiative and FSGS, into 4 sections and highlighted them below.

Kidney Compass: The PARASOL Initiative

Part 1: Introductions

Part 2: PARASOL Background and FSGS Landscape (Current Segment)

Part 3: PARASOL Findings and Implications for FSGS

Part 4: Future of PARASOL, FSGS Management

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.