OBJECTIVES: Manufacturers running trials for new therapies for CKD can face multiple challenges, including the lack of validated kidney-specific surrogate endpoints; this leads to longer and more expensive clinical trials and discourages manufacturers from developing new treatments. In the last few years, two potential surrogates for long-term renal outcomes have emerged: estimated glomerular filtration rate (eGFR) slope and proteinuria.

METHODS: CT.gov entries listed between January 2020 and December 2023 were reviewed to identify industry-led clinical trials that leveraged either eGFR slope or proteinuria as a clinical endpoint. Trends in the use of these endpoints were identified and analyzed.

RESULTS: 36 trials were identified listing eGFR slope, and 116 trials were identified listing proteinuria. Of the trials listing eGFR slope as an endpoint, 53% are ongoing. Of the ongoing trials, 68% are Phase 3, and the majority (37%) are in CKD. Other indications include immunoglobulin A (IgA) neuropathy, focal segmental glomerulosclerosis (FSGS), and diabetes. Of the trials listing proteinuria as an endpoint, 54% are ongoing. Of the ongoing trials, roughly the same proportion are Phase 2 or Phase 3 (41% and 43%, respectively). While indications included CKD, proteinuria was more commonly listed as clinical endpoints in more rare renal indications including lupus nephritis, C3 glomerulopathy, and IgA neuropathy.

CONCLUSIONS: Surrogate endpoints such as eGFR slope and proteinuria are increasingly being leveraged in Phase 2 and Phase 3 trials. Proteinuria is more frequently listed than eGFR slope, but the latter is more likely to be used in trials for CKD, whereas proteinuria is more often used in rarer renal indications. Given the increased use of these endpoints over time, both endpoints are likely to be used to support HTA decision-making in the next 3–5 years.