Authors' Reply: Unlocking the Potential of SC0062: A New Horizon in IgA Nephropathy Treatment?

We thank Xiong and Zhao1 for their interest in our JASN article about the albuminuria-lowering effects of the selective endothelin receptor antagonist SC0062 in patients with IgA nephropathy.2 Our trial enrolled participants with a biopsy-proven IgA nephropathy with similar inclusion criteria compared with other recent clinical trials that enrolled patients with IgA nephropathy.3–5 We did not record Oxford mesangial hypercellularity, endocapillary hypercellularity, segmental glomerulosclerosis, tubular atrophy/interstitial fibrosis, crescents scores as the main goal of the study was to find optimal doses of SC0062 for future phase 3 clinical trials. In these future trials, we will consider collection of Oxford mesangial hypercellularity, endocapillary hypercellularity, segmental glomerulosclerosis, tubular atrophy/interstitial fibrosis, crescents scores. Since our trial was a phase 2 dose-finding trial of 24-week duration, we were unable to assess the longer-term efficacy and safety of SC0062, which is the main objective of a recently started phase 3 clinical trial in participants with IgA nephropathy (NCT06819826). This trial will also enroll more patients with a GFR below 60 ml/min per 1.73 m2 to assess the efficacy and safety of SC0062 in people with more severe kidney impairment. Finally, the finding that the albuminuria-lowering effects were consistent in participants using and not using sodium-glucose cotransporter 2 inhibitors is in keeping with the results from clinical trials with other endothelin receptor antagonists, including atrasentan and zibotentan.4,6 We therefore do not consider our results a chance finding because of the small sample size. We agree that larger clinical trials, such as the ongoing SC0062 phase 3 trial, will provide more robust evidence.