Kidney Week

Abstract: SA-OR103

SC0062, a New Selective Endothelin Receptor Type A Antagonist in IgA Nephropathy

Session Information

• Late-Breaking Science Orals - 2
  October 26, 2024 | Location: Room 6C, Convention Center
  Abstract Time: 05:30 PM - 05:40 PM

Category: Glomerular Diseases

• 1402 Glomerular Diseases: Clinical, Outcomes, and Therapeutics

Authors

• Heerspink, Hiddo Jan L., Universitair Medisch Centrum Groningen Afdeling Klinische Farmacie en Farmacologie, Groningen, Groningen, Netherlands

Hiddo Jan L. Heerspink, PhD

• Du, Xiaoying, The First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, China

Xiaoying Du

• Xu, Yan, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China

Yan Xu

• Zhang, Yanning, General Hospital of Northern Theatre command, Shenyang, Liaoning, China

Yanning Zhang, PhD

• Liu, Bin, Wuxi People's Hospital, Wuxi, Jiangsu, China

Bin Liu, MD

• Bi, Guangyu, Northern Jiangsu People's Hospital, Yangzhou, Jiangsu, China

Guangyu Bi

• Xu, Chengyun, Nanchang University Second Affiliated Hospital, Nanchang, Jiangxi, China

Chengyun Xu

• Luo, Qun, Ningbo No 2 Hospital, Ningbo, Zhejiang, China

Qun Luo, MD

• Wu, Henglan, First Hospital of Jiaxing, Jiaxing, Zhejiang, China

Henglan Wu, MD

• Wan, Jianxin, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, China

Jianxin Wan, MD

• Cao, Liou, Jiading District Central Hospital Affiliated Shanghai University of Medicine & Health Sciences, Shanghai, China

Liou Cao, PhD

• Wang, Rong, Shandong Provincial Hospital, Jinan, Shandong, China

Rong Wang

• Fan, Qiuling, Shanghai General Hospital, Shanghai, Shanghai, China

Qiuling Fan, MD

• Cheng, Hong, Beijing Anzhen Hospital Affiliated to Capital Medical University, Beijing, China

Hong Cheng, DrMed

• Xu, Lixia, Guangdong Provincial People's Hospital, Guangzhou, Guangdong, China

Lixia Xu, MD

• Huang, Jiyi, The First Affiliated Hospital of Xiamen University, Xiamen, Fujian, China

Jiyi Huang

• Zhong, Aimin, Jiangxi Provincial People's Hospital, Nanchang, Jiangxi, China

Aimin Zhong, MBBS

• Peng, Qingfeng, Zhuzhou Central Hospital, Zhuzhou, Hunan, China

Qingfeng Peng

• Hei, Yongjiang, Biocity Biopharmaceutics Co., Ltd., Wuxi, Jiangsu, China

Yongjiang Hei

• Wang, Yiwei, Biocity Biopharmaceutics Co., Ltd., Wuxi, Jiangsu, China

Yiwei Wang, PhD, MD

• Zhou, Bo, Biocity Biopharmaceutics Co., Ltd., Wuxi, Jiangsu, China

Bo Zhou

• Zhang, Liqin, Biocity Biopharmaceutics Co., Ltd., Wuxi, Jiangsu, China

Liqin Zhang

• Chen, Jianghua, The First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, China

Jianghua Chen

Group or Team Name

• 2-SUCCEED Study Group & BioCity Team.

Background

Endothelin-1 upregulation and endothelin receptor type A (ETA) activation causes proteinuria, kidney inflammation and fibrosis in patients with IgA nephropathy (IgAN). A phase 2 trial was designed to characterize the efficacy, safety and optimal doses of SC0062 in patients with IgAN (2-SUCCEED, NCT05687890).

Methods

We conducted a randomized placebo-controlled double-blind trial in adults with biopsy proven IgAN and eGFR ≥30 mL/min/1.73m² with urinary protein: creatinine ratio (UPCR) ≥0.75 g/g or proteinuria ≥1 g/24h despite using maximum tolerated doses of ACEIs or ARBs. Patients were randomized 1:1:1:1 to SC0062 5, 10, 20 mg or matching placebo once daily. The primary efficacy outcome was percent change from baseline in UPCR in 24h urine samples after 12 weeks of treatment. Secondary endpoints included changes in eGFR over time. Safety outcomes including treatment emerging adverse events (TEAE) and serious adverse events (SAE) were recorded throughout the trial.

Results

A total of 131 patients (mean age 42 years [standard deviation (SD) 11]; mean eGFR 72 mL/min/1.73 m² [SD 24] and median 24h UPCR 1.2 g/g [Q1-Q3 0.90-1.53] ) were randomized to placebo (n=34) or SC0062 5 mg (n=33), 10 mg (n=32), or 20 mg (n=32). SC0062 reduced UPCR versus placebo throughout the treatment period. At Week 12, placebo-corrected geometric mean changes (95% confidence interval) from baseline in UPCR with SC0062 5, 10, and 20 mg were −27.8% (−42.9, −8.6), −20.4% (−37.2, 0.8), and −38.1% (−51.3, −21.3), respectively. The proportion of participants with a reduction in UPCR ≥ 30% from baseline in the placebo, SC0062 5, 10 and 20 mg dose groups were 33.3%, 48.5%, 62.5%, and 71.0%, respectively. No differences in eGFR were observed among treatment groups. The proportion of participants with TEAEs or SAEs was balanced among treatment groups. The rates of peripheral edema were lower in the SC0062 5, 10 and 20 mg groups, at 3%, 0% and 0%, respectively, compared to 14.7% in the placebo group.

Conclusion

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.

Funding

• Commercial Support – Biocity Biopharmaceutics Co., Ltd., Research and Development Plan of "Ling Yan" of the Science Department of Zhejiang Province Technology (2023C03074), National Natural Science Foundation of China Project (U21A20350)