The PARASOL initiative has identified proteinuria as a robust surrogate endpoint for clinical trials in focal segmental glomerulosclerosis (FSGS), offering a potential solution to the challenge of lengthy follow-up periods required to measure kidney failure. The findings, derived from an analysis of 1600 FSGS patients, suggest that monitoring proteinuria levels could significantly expedite drug development and improve patient outcomes.
Challenges in FSGS Clinical Trials
Traditional FSGS trials often require decades of follow-up to assess kidney failure, a critical endpoint for drug approval. This extended timeframe poses significant hurdles for researchers and pharmaceutical companies. Surrogate endpoints, such as proteinuria reduction, offer a more feasible alternative, as demonstrated in trials for IgA nephropathy and chronic kidney disease. However, FSGS presents unique challenges due to its heterogeneity.
Daniel Gale, PhD, MB BChir, emphasized the importance of validating surrogate endpoints by demonstrating a strong link between their reduction and meaningful clinical improvements. "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."
PARASOL Initiative Findings
Laura Mariani, MD, MS, detailed the PARASOL initiative's findings, noting that GFR variability was too high for practical use in trials. However, proteinuria emerged as a reliable predictor of kidney failure. "An analysis of 1600 FSGS patients, results suggested GFR variability was too high for practical use in trials. Proteinuria, however, emerged as a robust predictor of kidney failure," Mariani stated.
Proteinuria as a Surrogate Endpoint
The study revealed that patients achieving proteinuria levels below 0.7 g/g had a dramatically reduced risk of kidney failure, with a hazard ratio of 0.15, comparable to complete remission. This suggests that proteinuria could serve as a valuable surrogate endpoint, enabling smaller and faster trials. "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," Mariani explained.
Implications for Future Research
The identification of proteinuria as a surrogate endpoint has significant implications for future FSGS research. By using proteinuria levels as a key indicator, researchers can conduct more efficient trials, accelerating the development of new therapies and ultimately improving outcomes for patients with FSGS.
