SC0062 Effective and Safe in Patients With IgA Nephropathy

In patients with IgA nephropathy (IgAN) there are associations between both endothelin-1 upregulation and endothelin receptor type A (ETA) activation and proteinuria, inflammation, and fibrosis. The 2-SUCCEED trial was designed to identify the efficacy, safety, and optimal doses of SC0062 for the treatment of patients with IgAN (NCT05687890).

During a late-breaking oral session at ASN Kidney Week 2024, Hiddo Jan L. Heerspink, PhD, PharmD, reported results of the phase 2, randomized, placebo-controlled, double-blind trial. The presentation was titled SC0062, a New Selective Endothelin Receptor Type A Antagonist in IgA Nephropathy.

Study participants included adults with biopsy-proven IgAN and eGFR ≥30 mL/min/1.73 m² with urinary protein-creatinine ratio (UPCR) ≥75 g/g or proteinuria ≥1 g/24 hours. Eligible patients were being treated with maximum tolerated doses of angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers. Participants were randomized 1:1:1:1 to receive SC0062 at 5 mg, 10 mg, or 20 mg or matching placebo once daily.

The primary outcome of interest was the percentage change from baseline in UPCR in 24-hour urine samples following 12 weeks of treatment. Change in eGFR over time was a secondary outcome. Treatment-emergent adverse events and serious adverse events were recorded throughout the study period.

The overall study cohort included 131 patients with a median age of 42 years, mean eGFR 72 mL/min/1.73 m², and median 24-hour UPCR 1.2 g/g. The four study arms were SC0062 5 mg (n=33), SC0062 10 mg (n=32), SC0062 20 mg (n=32), and placebo (n=34).

Throughout the treatment period, there were reductions in UPCR with SC0062 versus placebo. At week 12, the placebo-corrected geometric mean changes in UPCR from baseline were –27.8% in the 5 mg arm, –20.4% in the 10 mg arm, and –38.1% in the 20 mg arm. The proportion of participants with a reduction in UPCR ≥30% from baseline was 33.3% in the placebo arm, 48.5% in the 5 mg arm, 62.5% in the 10 mg arm, and 71.0% in the 20 mg arm. There were no differences in eGFR among the treatment groups.

In safety analyses, the proportion of participants with treatment-emergent adverse events or serious adverse events was balanced among the groups. The rates of peripheral edema were 3%, 0%, and 0% in the SC0062 5 mg arm, 10 mg arm, and 20 mg arm, respectively, compared with 14.7% in the placebo arm.

The authors said, “In patients with IgA nephropathy and significant proteinuria, the novel ETA selective antagonist SC0062 showed a clinically meaningful reduction in proteinuria and a favorable safety profile with no risk of peripheral edema.”

Source: Heerspink HJL, Du X, Xu Y, et al. SC0062, a new selective endothelin receptor type A antagonist in IgA nephropathy. SA-OR103. Abstract of an oral presentation at the American Society of Nephrology Kidney Week 2024; October 26, 2024; San Diego, California. Funding for the study was provided by Biocity Biopharmaceutics Co., Ltd.