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).