BioCity Biopharma's SC0062, a selective endothelin receptor type A (ETA) antagonist, has demonstrated promising results in reducing proteinuria in patients with IgA Nephropathy (IgAN). The findings from the 2-SUCCEED Phase II clinical trial were presented at the American Society of Nephrology (ASN) Kidney Week 2024 and published in the Journal of the American Society of Nephrology (JASN). The multi-center, randomized, double-blind, placebo-controlled study evaluated the efficacy and safety of SC0062 in IgAN patients at high risk of disease progression, including those receiving SGLT2 inhibitors.
Key Findings from the 2-SUCCEED Trial
The 2-SUCCEED trial randomized 131 patients in a 1:1:1:1 ratio to receive either SC0062 at doses of 5 mg, 10 mg, or 20 mg, or placebo once daily for 24 weeks. The primary endpoint was the change in 24-hour urine protein-to-creatinine ratio (UPCR) from baseline to week 12.
At week 12, the SC0062 groups showed significant reductions in UPCR compared to placebo. Specifically, the geometric mean reductions from baseline in 24-hour UPCR were 39.2%, 33.7%, and 48.3% for the 5 mg, 10 mg, and 20 mg SC0062 groups, respectively, compared to 16.5% in the placebo group.
Secondary Endpoint Achievements
The study also met its secondary endpoints. At week 24, subjects receiving SC0062 at doses of 5 mg, 10 mg, and 20 mg had geometric mean reductions from baseline in 24-hour UPCR of 39.5%, 46.1%, and 62.3%, respectively, compared to 22.1% in the placebo group. The proportion of subjects achieving greater than a 30% reduction in UPCR at week 12 was 48.5%, 62.5%, and 71.0% in the SC0062 groups, compared to 33.3% in the placebo group.
Subgroup Analysis and Renal Function
A subgroup analysis showed that SC0062 consistently reduced UPCR regardless of whether patients were also receiving SGLT2 inhibitors. The proportion of subjects receiving SGLT2 inhibitors ranged from 46% to 47% across the four groups. Furthermore, SC0062 did not cause an acute decline in estimated glomerular filtration rate (eGFR), and eGFR values remained stable over the 24-week treatment period.
Safety and Tolerability
SC0062 was well-tolerated, with no increase in peripheral edema or fluid retention compared to placebo. The rates of edema for placebo and SC0062 at 5 mg, 10 mg, and 20 mg were 15%, 6%, 3%, and 3%, respectively. The treatment also did not result in weight gain or an increase in NT-pro-BNP levels.
Expert Commentary
Dr. Hiddo Lambers Heerspink, who presented the results at ASN, stated, "The significant and sustained reduction in urine protein excretion with SC0062, along with its notable safety advantages compared to other treatments, support a larger and long-term clinical trial in subjects with various types of CKD including IgA nephropathy. We look forward to the results of further studies on this drug."
About SC0062
SC0062 is a highly selective ETA antagonist being developed by BioCity for IgAN, diabetic kidney disease (DKD), and other types of chronic kidney disease (CKD). Its selectivity for ETA over endothelin receptor B (ETB) may offer advantages over non-selective ET antagonists, potentially reducing CKD progression while avoiding side effects associated with ETB blockade. SC0062 has been granted Breakthrough Therapy Designation by China's National Medical Products Administration (NMPA) for the treatment of IgAN with proteinuria.
