Amgen's cholesterol-lowering drug Repatha (evolocumab) has demonstrated significant long-term cardiovascular benefits in a pivotal Phase III trial, supporting the company's recently expanded FDA label for the PCSK9 inhibitor. The VESALIUS-CV trial (NCT03872401) met both its primary endpoints, proving that Repatha can significantly reduce the risk of major adverse cardiovascular events (MACE) in patients without a prior history of heart attack or stroke.
Trial Design and Results
The VESALIUS-CV trial enrolled more than 12,000 high-risk patients who were followed for 4.5 years. Of those enrolled, approximately 85% were maintained on a high-intensity or moderate LDL-C reducing therapy. The trial's primary endpoints were time to first occurrence of a composite of coronary heart disease (CHD) death, heart attack or ischemic stroke, and time to first occurrence of a composite of CHD death, heart attack, ischemic stroke or any ischemia-driven arterial revascularisation.
"The benefit across endpoints and established safety profile underscore Repatha's role as a cornerstone therapy in comprehensive lipid management," said Dr Jay Bradner, Amgen R&D executive vice-president. "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."
Regulatory Milestone and Market Impact
In August 2025, the US Food and Drug Administration approved the use of Repatha in adults at increased risk for major adverse cardiovascular events due to uncontrolled low-density lipoprotein cholesterol (LDL-C). The VESALIUS-CV trial data now provides clinical validation for this expanded indication.
Dr Bradner emphasized the potential reach of this expanded indication: "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."
Detailed trial data is scheduled to be presented at the American Heart Association Scientific Sessions on 8 November.
Competitive Landscape
Repatha was first approved in the US for adults with high cholesterol who require further LDL-C reduction on 27 August 2015, following European approval as the first PCSK9 inhibitor to receive regulatory clearance worldwide. However, its long market presence means it is approaching the end of its patent-protected period, due to end in 2030, opening opportunities for biosimilars.
GlobalData predicts this patent cliff will impact Amgen's market dominance, with peak sales for Repatha reaching $3.87bn in 2029 before slowly declining to a forecasted $3.32bn in 2031.
The drug faces competition from Praluent (alirocumab), a PCSK9 inhibitor developed by Regeneron and Sanofi, with GlobalData forecasting Praluent sales to reach $880m in 2031. After Praluent's approval, Regeneron and Sanofi, and Amgen were embroiled in a patent dispute over the two therapies, with Amgen emerging victorious.
Additional competition comes from Novartis' Leqvio (inclisiran), a long-acting small-interfering RNA (siRNA) that degrades PCSK9. GlobalData predicts Leqvio sales will rise sharply, from $754m in 2024 to $3.98bn in 2031.
Emerging Therapies and Market Outlook
Several LDL-C-lowering drugs have recently shown promise, including LIB Therapeutics' lerodalcibep, AstraZeneca's AZD0780 and NewAmsterdam Pharma's obicetrapib, indicating continued innovation in the cholesterol management space.
GlobalData predicts the total dyslipidemia (high cholesterol) market will reach $15.53bn across seven major markets (US, France, Germany, Italy, Spain, UK, and Japan) by 2032, highlighting the significant commercial opportunity in cardiovascular risk reduction therapies.
