Welcome to Kidney Compass: Navigating Clinical Trials!

Kidney Compass: PARASOL Findings and Implications for FSGS

13:43 - Challenges in Using GFR as a Surrogate Outcome

17:28 - Exploring Proteinuria as a Surrogate Outcome

In this installment, the third in a 4-part series, hosts Brendon Neuen, MBBS, PhD, and Shikha Wadhwani, MD, MS, are joined by Laura Mariani, MD, MS, and Daniel Gale, PhD, MB BChir, to discuss the PARASOL Initiative’s efforts to establish surrogate endpoints for clinical trials in focal segmental glomerulosclerosis (FSGS).

To open the episode, Neuen contextualizes the challenge: FSGS trials require decades of follow-up to measure kidney failure, an endpoint critical to drug approval. Surrogate endpoints like proteinuria reduction offer a feasible alternative, as seen in IgA nephropathy and chronic kidney disease trials, but FSGS presents unique hurdles due to its heterogeneity.

Gale explains the distinction between clinical outcomes (e.g., kidney failure) and surrogate endpoints (e.g., proteinuria reduction or GFR slope). To validate a surrogate, strong evidence must link its reduction to meaningful clinical improvements. Moreover, the treatment effect must convincingly translate into long-term benefits, a high bar for regulatory approval.

Next, Mariani details PARASOL's findings. An analysis of 1600 FSGS patients, results suggested GFR variability was too higreath for practical use in trials. Proteinuria, however, emerged as a robust predictor of kidney failure. According to Mariani, patients achieving proteinuria levels below 0.7 g/g had a dramatically reduced risk of kidney failure (hazard ratio, 0.15), comparable to complete remission. These findings suggest proteinuria could serve as a surrogate endpoint, providing the foundation for smaller, faster trials.

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. 

PARASOL Findings and Implications for FSGS

 include AstraZeneca, Bayer, Boehringer and Ingelheim, Janssen, and others. Relevant disclosures for 

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 

 include Novartis, Alexion, Calliditas, Britannia, Vifor, Judo Bio, Adnovate, Sanofi, Anlylam, Boehringer Ingelheim, and Bayer.

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Kidney Compass: Navigating Clinical Trials

Hosted by Brendon Neuen, MBBS, PhD, and Shikha Wadhwani, MD, MS, Kidney Compass: Navigating Clinical Trials is a regular podcast exploring and breaking down the latest updates and nuances of clinical trials in nephrology. By listening to Kidney Compass, you'll get the guidance you need to navigate the changing landscape of clinical trials across the spectrum of kidney disease. 

The PARASOL Initiative aims to establish surrogate endpoints for clinical trials in focal segmental glomerulosclerosis (FSGS), addressing the challenge of long follow-up periods required to measure kidney failure. Surrogate endpoints like proteinuria reduction offer a feasible alternative, but FSGS's heterogeneity complicates validation. The initiative's analysis of 1600 FSGS patients found proteinuria to be a strong predictor of kidney failure, suggesting it could serve as a surrogate endpoint. This could enable smaller, faster trials, potentially accelerating drug approval processes for FSGS treatments.

In part 3 of 4 from this episode, the discussion focuses on establishing surrogate endpoints for clinical trials in focal segmental glomerulosclerosis.

Kidney Compass: PARASOL Findings and Implications for FSGS

Welcome to Kidney Compass: Navigating Clinical Trials!

Key Timestamps

Kidney Compass: The PARASOL Initiative

Part 1: Introductions

Part 2: PARASOL Background and FSGS Landscape

Part 3: PARASOL Findings and Implications for FSGS (Current Segment)

Part 4: Future of PARASOL, FSGS Management