Amgen announced that its Phase 3 VESALIUS-CV clinical trial met dual primary endpoints, demonstrating that Repatha (evolocumab) significantly reduced the risk of major adverse cardiovascular events (MACE) in individuals without a prior history of heart attack or stroke. The landmark study enrolled over 12,000 high-risk patients, with approximately 85% maintained on high-intensity or moderate low-density lipoprotein cholesterol (LDL-C) reducing therapy, followed for a median of approximately 4.5 years.
The achievement marks a significant milestone in cardiovascular disease prevention, as Repatha becomes the first and only PCSK9 inhibitor shown to reduce cardiovascular events in high-risk adults without prior heart attack or stroke. This expands the drug's proven efficacy beyond secondary prevention, where it previously demonstrated benefits in the 2017 FOURIER study for patients with established atherosclerotic disease.
Primary Endpoints Achievement
The VESALIUS-CV study met its dual primary endpoints with both statistically and clinically significant results. The primary endpoints measured time to first occurrence of a composite of coronary heart disease (CHD) death, heart attack or ischemic stroke, as well as time to first occurrence of a composite of CHD death, heart attack, ischemic stroke or any ischemia-driven arterial revascularization. No new safety signals were observed during the trial.
"These results mark an important milestone in the fight against cardiovascular disease, the leading cause of death worldwide," said Jay Bradner, M.D., executive vice president of Research and Development at Amgen. "The benefit across endpoints and established safety profile underscore Repatha's role as a cornerstone therapy in comprehensive lipid management."
Addressing Unmet Medical Need
Cardiovascular disease remains the leading cause of death worldwide, with heart attacks or strokes occurring every 40 seconds in the U.S., and 75% of those being first-time events. High LDL-C, or "bad" cholesterol, represents one of the most modifiable risk factors for heart attack and stroke. However, more than 80% of patients with high cardiovascular risk without a prior heart attack or stroke were not at recommended LDL-C levels of lower than 70 mg/dL after one year of follow-up, according to recent study data.
The VESALIUS-CV results demonstrate that adding Repatha to standard therapy of statins or other LDL-C lowering treatments significantly reduces cardiovascular events compared with standard therapy alone as primary prevention. This finding has the potential to reach tens of millions more patients earlier in their cardiovascular disease journey, before a life-altering event occurs.
Study Design and Patient Population
VESALIUS-CV was designed as a Phase 3, double-blind, randomized, placebo-controlled global clinical trial to evaluate the impact of LDL-C lowering with evolocumab on MACE in adults at high cardiovascular risk without prior heart attack or stroke. The study enrolled patients with known atherosclerotic cardiovascular disease (ASCVD) or high-risk diabetes, who 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, and were treated with optimized lipid-lowering therapy.
Participants were randomized to receive Repatha or placebo in addition to optimized lipid-lowering therapy. The median follow-up period of approximately 4.5 years provided robust long-term safety and efficacy data for this primary prevention population.
Regulatory and Clinical Context
Earlier this year, the U.S. Food and Drug Administration broadened the approved use of Repatha to include adults at increased risk for major adverse cardiovascular events due to uncontrolled LDL-C. Repatha was first approved in 2015 and has since been used by more than 6.7 million patients globally, making it the most extensively studied PCSK9 inhibitor with clinical and real-world evidence across diverse populations and cardiovascular risk profiles.
The clinical benefits and safety of Repatha have been studied for 15 years in 51 clinical trials with over 57,000 patients. The drug is approved in 74 countries, including the U.S., Japan, Canada and in all 28 countries that are members of the European Union.
Mechanism of Action
Repatha is a human monoclonal antibody that inhibits proprotein convertase subtilisin/kexin type 9 (PCSK9). The drug binds to PCSK9 and inhibits circulating PCSK9 from binding to the low-density lipoprotein (LDL) receptor (LDLR), preventing PCSK9-mediated LDLR degradation and permitting LDLR to recycle back to the liver cell surface. By inhibiting the binding of PCSK9 to LDLR, Repatha increases the number of LDLRs available to clear LDL from the blood, thereby lowering LDL-C levels.
Full results from the VESALIUS-CV trial will be presented at the American Heart Association Scientific Sessions on November 8 as part of the session "Groundbreaking Trials in Cardiometabolic Therapeutics," and will be submitted for publication in a peer-reviewed journal.
