Amgen announced on October 2, 2025, that the Phase 3 VESALIUS-CV trial successfully met its dual primary endpoints, establishing Repatha (evolocumab) as the first PCSK9 inhibitor to significantly reduce cardiovascular events in primary prevention settings. This randomized, double-blind, placebo-controlled study enrolled over 12,000 adults at high cardiovascular risk, including those with known atherosclerotic cardiovascular disease (ASCVD) or high-risk diabetes, but without prior myocardial infarction (MI) or stroke. Participants had elevated lipid levels (LDL-C ≥90 mg/dL, non-HDL-C ≥120 mg/dL, or apolipoprotein B ≥80 mg/dL) despite optimized lipid-lowering therapy, with approximately 85% on high- or moderate-intensity LDL-C reducing regimens like statins.
The primary endpoints assessed time to first occurrence of: (1) composite major adverse cardiovascular events (MACE) including coronary heart disease (CHD) death, MI, or ischemic stroke; and (2) expanded composite adding ischemia-driven arterial revascularization. Both endpoints showed statistically and clinically significant reductions with evolocumab versus placebo, following a median follow-up of about 4.5 years. This builds on the 2017 FOURIER trial, which confirmed Repatha’s benefits in secondary prevention for patients with established ASCVD and prior events.
Safety findings aligned with Repatha’s established profile, with no new concerns identified. The trial’s implications are profound, addressing the global burden of cardiovascular disease—the leading cause of death—by enabling earlier intervention in high-risk populations to prevent first events. Jay Bradner, MD, Amgen’s executive vice president of R&D, stated, “These results mark an important milestone… Repatha has the potential to reach tens of millions more patients earlier in their journey.” Full results will be presented at the American Heart Association Scientific Sessions on November 8, 2025. VESALIUS-CV, part of the PROFICIO program, underscores aggressive LDL-C lowering’s role in comprehensive lipid management, potentially influencing guidelines for primary prevention in ASCVD or diabetes patients.
