CHMP recommends expanding Repatha (evolocumab) use in the EU after the Phase 3 VESALIUS-CV trial showed significant reductions in first heart attack, stroke, and major cardiovascular events in high-risk adults.
Written By: Fariha Sameen, PharmD
Reviewed By: Pharmacally Editorial Team
Amgen has secured a positive opinion from the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) recommending an expanded indication for Repatha (evolocumab) to reduce cardiovascular risk in adults with established or high-risk atherosclerotic cardiovascular disease (ASCVD). If endorsed by the European Commission, the indication would broaden Repatha’s use to patients without a previous heart attack or stroke who remain at elevated cardiovascular risk despite standard lipid-lowering therapy.
The recommendation is supported by findings from the global Phase 3 VESALIUS-CV trial (NCT03872401), which showed that adding Repatha to maximally tolerated statins, with or without ezetimibe, significantly reduced the incidence of major adverse cardiovascular events (MACE). The decision could expand access to intensive LDL cholesterol (LDL-C) lowering in a population that remains vulnerable despite current treatment.
Repatha Targets PCSK9 to Lower LDL Cholesterol
Repatha is a fully human monoclonal antibody that inhibits proprotein convertase subtilisin/kexin type 9 (PCSK9), preventing degradation of LDL receptors on hepatocytes. By increasing LDL receptor availability, the therapy enhances clearance of circulating LDL cholesterol, a well-established and modifiable driver of atherosclerotic cardiovascular disease.
Cardiovascular disease remains the leading cause of death worldwide. Although European Society of Cardiology and European Atherosclerosis Society guidelines recommend aggressive LDL-C lowering according to cardiovascular risk, many patients continue to have LDL-C concentrations above recommended targets despite statins and other lipid-lowering therapies. Individuals with diabetes or established ASCVD who have not yet experienced a heart attack or stroke remain at substantial residual risk.
Phase 3 VESALIUS-CV Demonstrated Significant Reduction in First Cardiovascular Events
The VESALIUS-CV study was a randomized, double-blind, placebo-controlled global Phase 3 trial enrolling more than 12,000 adults with established ASCVD or high-risk diabetes who had no previous myocardial infarction or stroke. Eligible participants had LDL-C of at least 90 mg/dL, non-HDL cholesterol of at least 120 mg/dL, or apolipoprotein B of at least 80 mg/dL despite receiving maximally tolerated statin therapy with or without ezetimibe.
Patients received either evolocumab or placebo in addition to optimized lipid-lowering therapy and were followed for a median of approximately 4.6 years.
The trial met its primary efficacy objectives. Repatha reduced the risk of the three-point composite endpoint of coronary heart disease death, myocardial infarction, or ischemic stroke by 25%. It also reduced the broader four-point MACE endpoint, which included ischemia-driven arterial revascularization, by 19%. Notably, evolocumab lowered the risk of first myocardial infarction by 36%, supporting its role in primary prevention among high-risk patients.
A lipid sub study further demonstrated marked LDL-C reduction, with a median LDL-C level of 45 mg/dL in the evolocumab group compared with 109 mg/dL in the placebo arm.
The trial results were published in the New England Journal of Medicine in November 2025 and provide the clinical evidence supporting the current European regulatory review.
CHMP Opinion Reflects Expanding Evidence for Earlier LDL-C Intervention
According to Amgen Chief Medical Officer Paul Burton, M.D., Ph.D., the CHMP recommendation recognizes the growing evidence supporting intensive LDL-C lowering in patients who remain at high cardiovascular risk despite available therapies. He noted that Repatha is the only PCSK9 inhibitor to demonstrate a reduction in first major cardiovascular events in a Phase 3 clinical trial, potentially expanding preventive treatment options across Europe if the indication receives final approval.
Repatha has been authorized in the European Union since 2015 for primary hypercholesterolemia, mixed dyslipidemia, and cardiovascular risk reduction in adults with established ASCVD. The positive CHMP opinion represents the next regulatory step toward extending its use to a broader population before the occurrence of a first heart attack or stroke.
European Commission Decision Expected in the Coming Months
The European Commission will now review the CHMP recommendation before issuing a final legally binding decision applicable across European Union Member States. If approved, the expanded indication would strengthen Repatha’s role in preventive cardiovascular care by supporting earlier intervention in high-risk adults with persistent LDL-C elevation despite optimized standard therapy.
The regulatory milestone also reinforces the growing clinical evidence supporting PCSK9 inhibition as an effective strategy for reducing first major cardiovascular events in patients with elevated residual cardiovascular risk.
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About the Writer
Fariha Sameen, PharmD (LinkedIn), is a clinical pharmacy professional with hands-on experience in patient counselling, medication review, therapeutic monitoring, and clinical documentation across multiple departments. She has experience identifying and assessing drug-related problems and supporting medication safety practices. Her interests include pharmacovigilance, ADR reporting, clinical research, and medical writing focused on clear, evidence-based communication.