PARASOL SCIENTIFIC WORKSHOP

The FDA and NephCure, ISGD, KHI, and NKF have expressed a willingness to leverage their combined strengths for the joint development of the substantive actions of this workshop to facilitate the development of safe and effective treatments for focal segmental glomerulosclerosis (FSGS).

FSGS is an important cause of kidney failure for which there are no FDA-approved therapies. Because of the time course for disease progression, rarity, and heterogeneity of FSGS, endpoints such as kidney failure are generally not feasible in clinical trials of FSGS. In 2019, the Kidney Health Initiative, a public-private partnership between the American Society of Nephrology and the FDA, initiated a project to identify endpoints that could be used to establish the efficacy of treatments for FSGS. The workgroup concluded that the available data support the use of complete remission of proteinuria in patients with heavy proteinuria as a surrogate endpoint for progression to kidney failure in clinical trials of FSGS. In addition, the workgroup concluded that substantial treatment effects on proteinuria short of a complete remission may also predict the effect of a treatment on progression to kidney failure; however, further work is needed to determine how such an endpoint should be defined. Specifically, to support the use of proteinuria as a reasonably likely surrogate endpoint, a better understanding of the quantitative relationship between changes in proteinuria and progression to kidney failure is needed.

The aforementioned project focused on information available in the published literature. To advance the understanding and use of proteinuria and eGFR-based endpoints as surrogate endpoints for accelerated and traditional approval in FSGS, NephCure, ISGD, KHI and NKF are facilitating new analyses of existing data from randomized controlled trials, observational studies, and registries. 

Currently, the work group is using the available data in FSGS to:

• Understand the utility and feasibility of eGFR as an endpoint for traditional approval or as a confirmatory endpoint for accelerated approval in FSGS. The goal of these analyses is to understand variability in FSGS and the associated impact on clinical trial design, specifically sample size requirements for achievable treatment effects.
• Model associations between new proteinuria-based endpoints (which may include additional variables) and clinical outcomes (e.g., kidney failure or death). The goal of these analyses is to identify endpoints other than a “complete remission of proteinuria” with sufficient ability to predict important clinical outcomes that could be used as a basis for traditional approval in clinical trials of FSGS.

The results of these analyses will be discussed at a scientific workshop, co-sponsored by the parties listed above. The statistical findings and report on the deliberations from the workshop will be made public by one or more publications in professional journals.

The goal of this scientific workshop is to advance the understanding of proteinuria and eGFR-based endpoints as surrogate endpoints for accelerated and traditional approval of new treatments for FSGS. The workshop will be used to discuss the results of the aforementioned analyses and engage in a data-driven discussion with the larger community about the use of these endpoints as surrogate endpoints for the approval of treatments for FSGS.