VESALIUS-CV: Evolocumab (Repatha) Achieves Primary Endpoints in Patients with ASCVD

The phase 3 VESALIUS-CV trial has achieved its dual primary endpoints, demonstrating a significant reduction in major adverse cardiovascular event (MACE) risk due to evolocumab (Repatha) in patients with atherosclerotic cardiovascular disease (ASCVD) and no prior history of heart attack or stroke.1

Announced by Amgen on October 2, 2025, VESALIUS-CV met the endpoints of time to first occurrence of a composite of heart attack, ischemic stroke, and coronary heart disease (CHD) death, as well as time to first occurrence of a composite of CHD death, ischemic stroke, heart attack, or any ischemia-driven arterial revascularization. Both endpoints were clinically and statistically significant, and no new safety signals were observed.1

“These results mark an important milestone in the fight against cardiovascular disease, the leading cause of death worldwide,” Jay Bradner, MD, executive vice president of research and development at Amgen, said in a statement. “The benefit across all endpoints and established safety profile underscore Repatha’s role as a cornerstone therapy in comprehensive lipid management.”1

The double-blind, randomized, placebo-controlled VESALIUS-CV trial enrolled >12,000 adult patients with known ASCVD or high-risk diabetes. The trial was begun after the 2017 FOURIER study proved the association between evolocumab and a reduction of MACEs in patients with established ASCVD and a history of MACEs, such as heart attack or stroke.1

All participants had no history of heart attack or stroke, an LDL-C ≥90 mg/dL, or non-high-density lipoprotein cholesterol (non-HDL-C) ≥120 mg/dL, or apolipoprotein B ≥80 mg/dL. Participants were randomly assigned to receive either evolocumab or placebo, along with optimized lipid-lowering therapy, and were followed for an approximate median of 4.5 years.1

Evolocumab is a monoclonal antibody that binds to proprotein convertase subtilisin/kexin type 9 (PCSK9), inhibiting circulating PCSK9 from binding to the low-density lipoprotein (LDL) receptor. This prevents PCSK9-mediated receptor degradation and allows the receptors to recycle back to the liver cell surface. This in turn increases the number of LDL receptors available to clear LDL from the blood, lowering overall LDL-C levels.1

Evolocumab was first approved by the US Food and Drug Administration (FDA) in 2015 to reduce MACEs in patients with increased risk of these events, as well as serving as an adjunct to diet and exercise in reducing LDL-C in patients with hypercholesterolemia or heterozygous familial hypercholesterolemia (HeFH). Its label was broadened in April 2025 to include patients with homozygous familial hypercholesterolemia (HoFH).2

“Repatha is known as a highly effective LDL-C lowering treatment and is now the first and only PCSK9 inhibitor shown to reduce cardiovascular events in high-risk adults without prior heart attack or stroke,” Bradner said. “These additional data demonstrate that Repatha has the potential to reach tens of millions more patients earlier in their journey, before a life-altering event occurs.”1

According to the press release, Amgen plans to present full results from the trial at the American Heart Association Scientific Sessions on November 8, 2025. Results will also be submitted for publication in a peer-reviewed journal simultaneously.1

References

1. Amgen. Landmark Phase 3 Trial (VESALIUS-CV) Meets Primary Endpoints in a Cardiovascular Primary Prevention Study of 12,000 Patients. PRNewswire. October 2, 2025. Accessed October 2, 2025. https://www.prnewswire.com/news-releases/landmark-phase-3-trial-vesalius-cv-meets-primary-endpoints-in-a-cardiovascular-primary-prevention-study-of-12-000-patients-302573412.html

2. Repatha Now Indicated for Adults at Increased Risk for Major Adverse Cardiovascular Events Due to Uncontrolled LDL-C. Amgen. August 25, 2025. Accessed October 2, 2025. https://www.amgen.com/newsroom/press-releases/2025/08/repatha-now-indicated-for-adults-at-increased-risk-for-major-adverse-cardiovascular-events-due-to-uncontrolled-ldl-c