Efficacy and Safety of Alirocumab in Reducing Lipids and Cardiovascular Events (ODYSSEY LONG TERM)

The ODYSSEY LONG TERM trial randomized 2,341 high-risk patients (ASCVD or heterozygous familial hypercholesterolemia) on maximally tolerated statin therapy to alirocumab 150 mg every 2 weeks or placebo for 78 weeks, with safety and LDL-C reduction as primary outcomes and an exploratory cardiovascular endpoint analysis.

Alirocumab reduced LDL-C by 62% at 24 weeks with sustained reduction through 78 weeks. At post-hoc analysis, major adverse cardiovascular events occurred in 1.7% of alirocumab versus 3.3% of placebo patients — a 48% relative reduction (HR 0.52, p=0.02), though this was a post-hoc exploratory analysis with a small event count.

ODYSSEY LONG TERM established alirocumab’s long-term safety profile and its degree of LDL-C reduction in a high-risk population. The exploratory cardiovascular signal was hypothesis-generating for the definitive ODYSSEY Outcomes trial, which subsequently confirmed cardiovascular event reduction in a larger post-ACS population.

Alirocumab and evolocumab produce similar degrees of LDL-C reduction through the same mechanism (PCSK9 antibody inhibition). Both have now demonstrated cardiovascular event reduction in phase 3 outcomes trials, establishing the PCSK9 inhibitor class as the definitive second-line lipid-lowering therapy after maximal statins.

We rate the evidence strong for lipid-lowering; the cardiovascular endpoint result was exploratory. A key long-term safety and efficacy trial establishing alirocumab’s 62% LDL-C reduction profile — foundational data informing the subsequent ODYSSEY Outcomes trial.