Efficacy and Safety of Quarterly Dosing SHR-1918 in Patients With Suboptimally Controlled Hyperlipidemia

BACKGROUND: SHR‐1918 is a long‐acting angiopoietin‐like 3 antibody with established lipid‐lowering efficacy at 600 mg once every 4 weeks or once every 8 weeks. OBJECTIVES: This randomized, double‐blind, placebo‐controlled study assessed the efficacy and safety of SHR‐1918 at an extended dosing interval (once every 12 weeks) in patients with hyperlipidemia. METHODS: Patients who did not achieve their low‐density lipoprotein cholesterol (LDL‐C) targets after statin run‐in were randomized (2:1) to receive subcutaneous SHR‐1918 (600 or 1,200 mg) or placebo once every 12 weeks for 24 weeks. The primary endpoint was percent change in LDL‐C from baseline to week 24. RESULTS: Forty‐four patients were randomized to SHR‐1918 600 mg (n = 14), SHR‐1918 1,200 mg (n = 16), or placebo (n = 14). At week 24, the percent change in LDL‐C from baseline was ‐20.8% (95% CI: ‐28.4 to ‐13.1), ‐25.1% (95% CI: ‐32.4 to ‐17.7), and ‐2.2% (95% CI: ‐10.1 to 5.7) in the 3 groups, respectively. The between‐group difference (SHR‐1918 vs placebo) was ‐18.6% (95% CI: ‐29.5 to ‐7.6; P = 0.0015) for 600 mg and ‐22.9% (95% CI: ‐33.7 to ‐12.1; P = 0.0001) for 1,200 mg. The percent change in triglyceride was ‐49.8% (95% CI: ‐61.7 to ‐37.9) and ‐58.8% (95% CI: ‐70.3 to ‐47.3) with SHR‐1918 600 mg and 1,200 mg compared with ‐1.2% (95% CI: ‐13.6 to 11.2) with placebo, showing between‐group differences of ‐48.6% (95% CI: ‐65.8 to ‐31.4; P < 0.0001) and ‐57.6% (95% CI: ‐74.6 to ‐40.6; P < 0.0001). CONCLUSIONS: SHR‐1918, at a once every 12 weeks dosing frequency, further reduced LDL‐C and triglyceride levels in hyperlipidemic patients inadequately controlled with background lipid‐lowering therapies. (Evaluation of the Efficacy and Safety of Multiple Subcutaneous Injections of SHR‐1918 in Patients With Hyperlipidemia in Poor Control; NCT06471218).