Key result
SHR-1918 cuts LDL-C by up to ~30% vs placebo in patients with suboptimally controlled hyperlipidemia.
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Why the study?
The lipid-altering efficacy and safety of the ANGPTL-3 monoclonal antibody SHR-1918 in patients at moderate or higher ASCVD risk with suboptimally controlled hyperlipidemia required evaluation.
RCT (n=333)
Double-blind
4:1 (active/placebo)
Yes
Captured external expert commentary on this paper, strongest first. Original sources are linked where available.
“The core advantage of SHR-1918 lies in its unique target of action by inhibiting ANGPTL-3 while enhancing the activity of LPL and EL, which achieves dual regulation of LDL-C and TG. The findings of this study support that SHR-1918 could be a novel treatment option for patients with moderate or higher risk of ASCVD who have not achieved optimal lipid control and need additional lipid reduction beyond statins and other lipid-lowering therapies.”
“There are other new targets emerging, one of which is elevated triglycerides and remnant cholesterol, and this is being targeted now with some additional drugs in development. These include agents targeting apolipoprotein CIII (APOC3), which is involved in triglyceride metabolism, and ANGPTL3, which is also being studied in some trials for hypertriglyceridemia. Although we have yet to show that these triglyceride-lowering drugs can reduce morbidity and mortality, they are promising.”
SHR-1918 adds 22-30% LDL-C and substantial TG reductions on standard therapy; extends phase 2 RCT evidence for ANGPTL3 inhibition in moderate/high-risk hyperlipidemia.
BACKGROUND Angiopoietin-like 3 (ANGPTL-3) inhibits the activity of lipoprotein lipase and endothelial lipase, increasing both serum low-density lipoprotein cholesterol (LDL-C) and triglyceride (TG) levels. SHR-1918 is a fully human monoclonal antibody against ANGPTL-3. OBJECTIVES The aim of this study was to assess the lipid-altering efficacy and safety of SHR-1918 in patients at moderate or higher risk of atherosclerotic cardiovascular disease (ASCVD) with suboptimally controlled hyperlipidemia. METHODS A multicenter, randomized, double-blind, placebo-controlled, dose-escalation phase 2 study was designed to evaluate the effects of SHR-1918 in hypercholesterolemic patients, who did not achieve optimal LDL-C after 4 to 8 weeks of standard lipid-lowering therapies. A total of 333 patients were enrolled sequentially into 1 of 8 dose cohorts at a 4:1 (active/placebo) ratio. Patients received subcutaneous SHR-1918 at doses of 150, 300, or 600 mg every 4 weeks (Q4W), or SHR-1918 at a dose of 600 mg every 8 weeks (Q8W), alternating with placebo for a total treatment period of 16 weeks. The extension treatment included subcutaneous SHR-1918 at a dose of 150, 300, or 600 mg Q4W over 36 weeks, or SHR-1918 a dose of 600 mg Q8W over 40 weeks and then followed for safety. Prespecified endpoints included percentage change from baseline in LDL-C and TG. Safety was assessed with laboratory test results and by the incidence and severity of adverse events. RESULTS SHR-1918 demonstrated a clear dose-response relationship with respect to percentage LDL-C lowering for both Q4W and Q8W administration: 21.7%, 27.3%, and 29.9% with 150, 300, and 600 mg Q4W compared with placebo, respectively, and 22.5% with 600 mg Q8W compared with placebo. SHR-1918 also substantially reduced TG, non-high-density lipoprotein cholesterol, apolipoprotein B, and apolipoprotein A1, with a better achievement of LDL-C targets. SHR-1918 was generally well-tolerated. CONCLUSIONS Based on standard lipid-lowering therapy, ANGPTL-3 inhibition with SHR-1918 further reduces LDL-C by 21.7% to 29.9% in patients at moderate or higher risk of ASCVD. These additional reductions are both dose and dosing frequency dependent. (Evaluate the Efficacy and Safety of SHR-1918 in Patients With Hyperlipidemic; NCT06109831).
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Xie et al. (2025) conducted an RCT in Suboptimally controlled hyperlipidemia (n=333). SHR-1918 vs. Placebo was evaluated on Percentage change from baseline in LDL-C and TG. SHR-1918 reduced LDL-C by 21.7% to 29.9% compared with placebo in patients at moderate or higher risk of ASCVD with suboptimally controlled hyperlipidemia.
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