Safety and efficacy of SHR4640 combined with febuxostat for primary hyperuricemia: a multicenter, randomized, double-blind, phase II study

Honghu Tang; Beibei Cui; Yiyu Chen; Lin Chen; Zhihong Wang; Ning Zhang; Yanlan Yang; Xiaodong Wang; Xiangliang Xie; Lingyun Sun; Wantai Dang; Xianyang Wang; Runzi Li; Jianjun Zou; Yi Zhao; Yi Liu

doi:10.1177/1759720X211067304

Safety and efficacy of SHR4640 combined with febuxostat for primary hyperuricemia: a multicenter, randomized, double-blind, phase II study

Ther Adv Musculoskelet Dis. 2022 Jan 31:14:1759720X211067304. doi: 10.1177/1759720X211067304. eCollection 2022.

Authors

Honghu Tang¹, Beibei Cui¹, Yiyu Chen¹, Lin Chen², Zhihong Wang³, Ning Zhang⁴, Yanlan Yang⁵, Xiaodong Wang⁶, Xiangliang Xie⁷, Lingyun Sun⁸, Wantai Dang⁹, Xianyang Wang¹⁰, Runzi Li¹⁰, Jianjun Zou¹⁰, Yi Zhao¹¹, Yi Liu¹¹

Affiliations

¹ Department of Rheumatology and Immunology, West China Hospital, Sichuan University, Chengdu, China.
² Department of Rheumatology and Immunology, Jilin Province People's Hospital, Changchun, China.
³ Department of Endocrinology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
⁴ Department of Rheumatology and Immunology, Shengjing Hospital of China Medical University, Shenyang, China.
⁵ Department of Endocrinology, Shanxi Provincial People's Hospital, Taiyuan, China.
⁶ Department of Rheumatology and Osteology, The First Affiliated Hospital of Clinical Medicine of Guangdong Pharmaceutical University, Guangzhou, China.
⁷ Department of Rheumatology and Immunology, Maanshan People's Hospital, Maanshan, China.
⁸ Department of Rheumatology and Immunology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China.
⁹ Department of Rheumatology and Immunology, The First Affiliated Hospital of Chengdu Medical College, Chengdu, China.
¹⁰ Clinical Research and Development, Jiangsu Hengrui Pharmaceuticals Co., Ltd. (formerly Jiangsu Hengrui Medicine Co., Ltd.), Shanghai, China.
¹¹ Department of Rheumatology and Immunology, West China Hospital, Sichuan University, No. 37 Guoxue Lane, Wuhou District, Chengdu 610041, China.

Abstract

Background: To evaluate the safety, tolerability, and efficacy of SHR4640, a highly selective urate transporter-1 inhibitor, in combination with febuxostat, in patients with primary hyperuricemia.

Methods: In this randomized, double-blind, parallel-controlled phase II study, patients whose fasting serum uric acid (sUA) levels were ⩾ 480 μmol/L at screening with gout or sUA levels were ⩾ 420 μmol/L lasting for at least 3 months without gout, either with sUA levels ⩾ 540 μmol/L at screening or sUA levels ⩾ 480 μmol/L with comorbidities at screening, were enrolled. Patients were randomized (1:1:1) to receive SHR4640 10 mg plus febuxostat 80 mg, SHR4640 10 mg plus febuxostat 40 mg, and SHR4640 5 mg plus febuxostat 20 mg orally once daily. The primary end point was the incidence of treatment-emergent adverse events (TEAEs).

Results: A total of 93 patients were randomized and received treatment. TEAEs occurred in 55.9% of patients. The incidence of TEAEs was comparable among all the groups. Serious TEAEs occurred in one patient (1.1%), with no deaths observed. The proportion of patients who achieved the target sUA levels by week 4 was 79.3%, 96.6%, and 75.0% in the SHR4640 10 mg plus febuxostat 80 mg, SHR4640 10 mg plus febuxostat 40 mg, and SHR4640 5 mg plus febuxostat 20 mg groups, respectively. The mean percent reduction of sUA was 59.7%, 63.7%, and 41.8%, respectively.

Conclusion: SHR4640 plus febuxostat exhibited a tolerable safety profile and substantial sUA lowering activity in patients with primary hyperuricemia.

Registration: www.chinadrugtrials.org.cn; CTR 20192429.

Keywords: SHR4640; URAT-1 inhibitor; XOIs; febuxostat; gout; primary hyperuricemia.