What is the Odyssey trial?

From the Guidelines

The ODYSSEY trial clearly demonstrates that alirocumab, a PCSK9 inhibitor, significantly reduces cardiovascular events in patients with recent acute coronary syndrome and elevated LDL cholesterol despite intensive statin therapy, with a 15% relative risk reduction in major adverse cardiovascular events (MACE) compared to placebo 1. The study found that patients who received alirocumab 75 mg subcutaneously every two weeks, with dose adjustment to 150 mg if LDL-C remained ≥50 mg/dL, achieved a mean LDL-C reduction of 54.7% from baseline. Key findings of the trial include:

• A composite primary end point (comprising death from CHD, nonfatal MI, fatal or nonfatal ischemic stroke, or unstable angina requiring hospital admission) occurred in 903 individuals (9.5%) in the alirocumab group and in 1,052 individuals (11.1%) in the placebo group (HR 0.85 [95% CI 0.78–0.93]; P < 0.001) 1.
• The greatest benefit was observed in patients with baseline LDL-C ≥100 mg/dL, who showed a significant relative risk reduction in MACE.
• Alirocumab was generally well-tolerated with injection site reactions being the most common adverse effect. This trial provides important evidence supporting the use of PCSK9 inhibitors as add-on therapy to statins in high-risk patients with elevated LDL-C, particularly those with recent acute coronary syndrome who need additional lipid-lowering beyond what statins alone can provide 1. In the context of statin intolerance, the ODYSSEY ALTERNATIVE trial also demonstrated the efficacy and safety of alirocumab compared to ezetimibe and atorvastatin in reducing LDL cholesterol levels in patients with primary hypercholesterolemia and statin intolerance, with a 54.8% reduction in LDL cholesterol levels compared to 20.1% with ezetimibe 1.

From the FDA Drug Label

Trial 7 (ODYSSEY CHOICE I, NCT01926782) was a multicenter, double-blind, placebo-controlled trial that randomly assigned 458 adult patients with primary hyperlipidemia to PRALUENT 300 mg every 4 weeks, 115 adult patients to PRALUENT 75 mg every 2 weeks, and 230 adult patients to placebo. The proportion of patients who discontinued trial drug prior to the 24-week primary endpoint was 10% among those treated with PRALUENT and 0% among those treated with placebo At week 12, the treatment difference between PRALUENT 300 mg every 4 weeks and placebo in mean percent change in LDL-C from baseline was -54% (97.5% CI: -61%, -48%), and the treatment difference between PRALUENT 75 mg every 2 weeks and placebo in mean percent change in LDL-C was -44% (97. 5% CI: -53%, -35%) At week 24, the treatment difference between initial assignment to PRALUENT 300 mg every 4 weeks and placebo in mean percent change in LDL-C from baseline was -56% (97.5% CI: -62%, -49%; p-value: <0.0001), and the treatment difference between initial assignment to PRALUENT 75 mg every 2 weeks and placebo in mean percent change in LDL-C from baseline was -48% (97. 5% CI: -57%, -39%).

The ODYSSEY trial showed that alirocumab (PRALUENT) significantly reduced LDL-C levels compared to placebo.

• The treatment difference in mean percent change in LDL-C from baseline at week 12 was -54% for PRALUENT 300 mg every 4 weeks and -44% for PRALUENT 75 mg every 2 weeks.
• The treatment difference in mean percent change in LDL-C from baseline at week 24 was -56% for PRALUENT 300 mg every 4 weeks and -48% for PRALUENT 75 mg every 2 weeks 2.

From the Research

Overview of the Odyssey Trial

• The Odyssey trial is a series of studies that evaluated the efficacy and safety of alirocumab, a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor, in patients with hypercholesterolemia.
• The trials included patients with heterozygous familial hypercholesterolemia (HeFH) or very-high low-density lipoprotein cholesterol (LDL-C) levels despite maximally tolerated dose of statin ± other lipid-lowering therapies (MTD ± LLTs) 3.
• The studies demonstrated that alirocumab was generally well-tolerated and resulted in clinically significant LDL-C reductions 3, 4, 5, 6, 7.

Efficacy of Alirocumab

• Alirocumab significantly reduced LDL-C levels from baseline to week 24, with a mean reduction of 47% to 54% 4, 5, 6.
• The treatment also reduced lipoprotein(a), non-high-density lipoprotein cholesterol, and apolipoprotein B levels from baseline to week 24 4.
• In patients with ASCVD, alirocumab reduced LDL-C levels by 45.6 to 64.8 mg/dL, regardless of prior revascularization status 4.

Safety of Alirocumab

• The overall incidence of treatment-emergent adverse events (TEAEs) was 71.6%, with common TEAEs including nasopharyngitis, myalgia, and headache 3.
• Injection-site reactions were among the most common treatment-emergent adverse events, occurring in <2% to 4% of patients 5, 6.
• Alirocumab had a similar safety profile regardless of revascularization status, with higher rates of injection-site reactions versus controls 4.

Patient Populations

• The Odyssey trials included patients with HeFH, very-high LDL-C levels, and ASCVD, with or without prior coronary revascularization 3, 4.
• The studies also included patients who were not on statin therapy, including those with statin-associated muscle symptoms 5, 7.
• Alirocumab was effective in reducing LDL-C levels in these patient populations, with a similar safety profile 3, 4, 5, 6, 7.