Today marks a turning point for people living with focal segmental glomerulosclerosis (FSGS). More than a hundred years after the disease was first defined, the U.S. Food and Drug Administration (FDA) has granted its first ever approval of a drug for FSGS—an achievement that many in the glomerular disease community have been working toward for years.
Behind this moment is not only the science of a single molecule, but also the science of how we evaluate treatments. The PARASOL project led by ISGD was created to answer a deceptively simple question: In FSGS, which biomarkers can reliably predict long-term kidney outcomes, and meet the high regulatory bar of serving as a validated surrogate endpoint for clinical trials? Clinicians have relied on proteinuria as a key marker of disease activity and risk, but until recently this practice lacked a unified, data‑driven framework robust enough to support registration‑quality endpoints. Meanwhile, the heterogeneous etiologies and variable progression rates of FSGS in a rare patient population made it logistically challenging and infeasible to conduct trials powered for ESKD or large, sustained eGFR declines.
The PARASOL initiative (Proteinuria and Other Biomarkers as Endpoints for Clinical Trials in Kidney Disease) was designed to address these questions and investigate whether early improvements in proteinuria or eGFR could reliably predict subsequent kidney health in FSGS patients. In collaboration with the FDA and co-sponsored by the International Society of Glomerular Disease, NephCure, the Kidney Health Initiative of the American Society of Nephrology, and the National Kidney Foundation, PARASOL convened multiple academic cohorts, registries, and other datasets to assemble a pooled FSGS cohort with sufficient size and longitudinal depth to rigorously examine how early changes in these biomarkers relate to long-term kidney survival for FSGS patients. Using a landmark modeling approach and investigating multiple definitions of response, PARASOL investigators demonstrated that achievement of lower proteinuria was consistently associated with lower subsequent risk of kidney failure.
In the words of primary investigator Laura Mariani, MD, “The PARASOL-FSGS initiative is really a success of the international nephrology community. Nephrologists across the world were willing to openly share data to answer a key question about the relationship between short term changes in eGFR and proteinuria with long term risk of kidney failure in FSGS. This is a question that is critical to the design and interpretation of clinical trials in FSGS, but also in other rare kidney diseases. The interdisciplinary contributions from clinicians, researchers, biostatistician, patients, industry and regulatory partners were key to designing relevant study questions.”
A defining feature of PARASOL is its inherently collaborative nature. The project simply would not have been possible without many stakeholders working together. ISGD’s Chief Medical and Strategy Officer Barbara Gillespie, MD said, “The FDA has been a unique and genuine partner with ISGD in analyzing and understanding how the collective PARASOL data supports proteinuria as an endpoint for FSGS clinical trials. The big win here is for our patients, who have waited over one hundred years for an approved treatment since FSGS was first described in 1925.”
Lead biostatistician Abigail Smith, PhD, commented, “Investments in longitudinal data collection are critical, particularly in diseases lacking established, effective treatments. PARASOL would not have been possible without the partnership of international registries that shared the data allowing us to draw robust conclusions about relationships that can be challenging to measure due to small numbers. The fact that we were able to use observational data to make strong arguments about proteinuria as a surrogate endpoint speaks to the value of the contributions from each individual registry, and how that value is amplified when combined with other data sources.”
For nephrologists and trialists, PARASOL offers a template. The same infrastructure and methods are now being extended to primary membranous nephropathy and APOL1 kidney disease, with analogous efforts to define and validate disease‑specific surrogate endpoints. The PARASOL working group is also probing additional proteinuria endpoint definitions and subgroup effects within FSGS, incorporating additional data, engaging in custom analyses to inform development programs, and using this experience to train the next generation of investigators. PARASOL continues to welcome new collaborators and partners; the steering committee can be reached at parasol@is-gd.org.
For patients and families, this approval means that FSGS is no longer a disease without any specifically approved treatment options. For the broader kidney community, it demonstrates that collaborative endpoint science can shorten the path between promising biology and real therapies.