Angiopoietin-Like 3 Antibody Therapy in Patients With Suboptimally Controlled Hyperlipidemia: A Phase 2 Study.

Summary

In a phase 2 randomized, double-blind trial of 333 patients with inadequately controlled hyperlipidemia on standard therapy, the ANGPTL-3 antibody SHR-1918 reduced LDL-C by 21.7–29.9% vs placebo with substantial triglyceride and apoB lowering and acceptable tolerability. Effects were dose- and interval-dependent (Q4W and Q8W).

Key Findings

• LDL-C reductions vs placebo: 21.7%, 27.3%, 29.9% with 150, 300, 600 mg Q4W; 22.5% with 600 mg Q8W.
• Marked decreases in triglycerides, non-HDL-C, apolipoprotein B, and apolipoprotein A1, with improved LDL-C target attainment.
• Generally well tolerated over 16 weeks with dose-dependent effects.

Clinical Implications

ANGPTL-3 antibodies may offer an option for patients not at LDL-C goal or with mixed dyslipidemia despite statins/ezetimibe/PCSK9i; long-term outcome trials, safety, and positioning vs evinacumab are needed.

Limitations

• Phase 2 duration; not powered for cardiovascular outcomes
• Population at moderate-to-high ASCVD risk but heterogenous background therapies

Future Directions

Phase 3 trials assessing hard cardiovascular outcomes, head-to-head comparisons with existing biologics (e.g., evinacumab), and evaluation in severe hypertriglyceridemia and statin-intolerant populations.