Novel ANGPTL-3 inhibitor lowers LDL-C in patients with higher ASCVD risk

Inhibition of angiopoietin-like 3 (ANGPTL-3) with SHR-1918 leads to further low-density lipoprotein cholesterol (LDL-C) reductions in patients at increased risk of atherosclerotic cardiovascular disease (ASCVD), a phase II study has shown.

“These additional reductions are both dose and dosing frequency dependent,” the authors said.

Treatment with SHR-1918 showed a clear dose-response association with percentage LDL-C lowering for administration every 4 weeks (Q4W) and every 8 weeks (Q8W): 21.7 percent with 150 mg, 27.3 percent with 300 mg, and 29.9 percent with 600 mg Q4W and 22.5 percent with 600 mg Q8W versus placebo.

In addition, SHR-1918 resulted in substantial reductions in triglycerides, nonhigh-density lipoprotein cholesterol, apolipoprotein B, and apolipoprotein A1, as well as better achievement of LDL-C targets. In terms of safety, the SHR-1918 was well-tolerated.

The authors conducted this multicentre, randomized, double-blind, placebo-controlled, dose-escalation phase II study to examine the effects of SHR-1918 in hypercholesterolaemic patients, who did not achieve optimal LDL-C after 4 to 8 weeks of standard lipid-lowering therapies.

Some 333 patients were enrolled into one of eight dose cohorts at a 4:1 ratio. They received subcutaneous SHR-1918 150, 300, or 600 mg Q4W, or SHR-1918 600 mg Q8W, alternating with placebo for 16 weeks. In the extension treatment, patients received SHR-1918 at a dose of 150, 300, or 600 mg Q4W over 36 weeks, or at a dose of 600 mg Q8W over 40 weeks. They were then followed for safety.

“ANGPTL-3 inhibits the activity of lipoprotein lipase and endothelial lipase, increasing both serum LDL-C and triglyceride levels,” the authors said. “SHR-1918 is a fully human monoclonal antibody against ANGPTL-3.”