ODYSSEY data mining

→ Video summary

→ Study background

→ Study details

→ Key baseline characteristics

→ Results

→ Safety

→ Additional resources

Watch Prof Perrone-Filardi's summary of the study:

Study background

• All patients with ASCVD are at very high or extreme risk of a potentially fatal CV event²
• LDL-C is the primary target for CV risk reduction and PCSK9 inhibitors such as PRALUENT can reduce LDL-C levels when used alone or in combination with statins^2,3+
• However, data on the effect of PCSK9 inhibitors on CV risk in patients with ASCVD without prior ACS or stroke are limited¹
• This post hoc pooled analysis sought to determine the efficacy and safety of PRALUENT in ASCVD patients who had not previously experienced a CV event¹

Study Details

What is data mining?

Data mining refers to the process of extracting potentially useful information, such as patterns or relationships, from large and complex datasets.⁴

Key baseline characteristics¹

Adapted from Castro Cabezas et al. 2025.

Efficacy results

Primary endpoint: PRALUENT demonstrated significant LDL-C reduction vs. placebo at leek 24 in ASCVD patients without previous ACS or stroke:^1,*

Absolute change in calculated LDL-C at Week 24 was -71.7 mg/dL for PRALUENT and -1.5 mg/dL for placebo.¹

The administration of PRALUENT resulted in a significantly greater reduction in LDL-C levels at Week 24 across all three pools:

Change in LDL-C levels from baseline to Week 24 per study group (ITT population)¹

Adapted from Castro Cabezas et al. 2025.

Secondary endpoints: from baseline to Week 12, PRALUENT was associated with a significant improvement in the percentage change in calculated LDL-C levels, ApoB and Lp(a) vs. ezetimibe or placebo¹

Least squared mean difference vs. placebo for patients treated with PRALUENT 150 mg Q2W in the ITT population¹

Adapted from Castro Cabezas et al. 2025.

Subgroup analyses: consistently greater LDL-C reduction with PRALUENT vs. ezetimibe or placebo achieved across patients with CAD + diabetes and established CADI

Safety results

PRALUENT was generally well tolerated, with a similar safety profile to control arms across all study groups

• TEAEs were experienced by 76.5% and 74.8% of patients and SAEs were experienced by 13.7% and 15.7% of patients in the ezetimibe and PRALUENT (75/150 Q2W) groups, respectively¹
• TEAEs were experienced by 78.9% and 81.4% of patients and SAEs were experienced by 19.4% and 18.6% of patients in the placebo and PRALUENT (75/150 mg or 150 mg Q2W) groups, respectively¹

Adverse event profile for ASCVD patients with CAD or PAD + diabetes or established CAD treated with PRALUENT vs. ezetimibe and placebo¹

Adapted from Castro Cabezas et al. 2025.

Indication, dosing and footnotes

This material is intended for healthcare professionals only.

PRALUENT (alirocumab) indication⁵

Primary hypercholesterolaemia and mixed dyslipidaemia

PRALUENT^® is indicated in adults with primary hypercholesterolaemia (heterozygous familial and non-familial) or mixed dyslipidaemia, and in paediatric patient 3 years of age and older with heterozygous familial hypercholesterolaemia (HeFH) as an adjunct to diet:

• in combination with the maximum tolerated dose of a statin with or without other lipid-lowering therapies or,
• alone or in combination with other lipid-lowering therapies in patients who are statin-intolerant, or for whom a statin is contraindicated

Dosing informations⁵

The recommended PRALUENT doses are 75 mg once every 2 weeks, 150 mg once every 2 weeks, 300 mg once every 4 weeks (monthly), administered subcutaneously. All doses may be used for initiation of treatment.

The dose of PRALUENT can be individualised based on patient characteristics, such as baseline LDL-C level, goal of therapy, and response to treatment. Lipid levels can be assessed 4 to 8 weeks after treatment initiation or titration, and dose adjusted accordingly (up-titration or down-titration). Intense LDL-C reduction is expected with PRALUENT 150 mg once every 2 weeks and 300 mg once every 4 weeks (monthly), where 150 mg once every 2 weeks is the maximum dose.

For the treatment of HeFH in paediatric patients 8 years of age and older:

- for patients with a body weight of less than 50 kg, the recommended dose is 150 mg once every 4 weeks and, if additional LDL-C reduction is needed, a dose of 75 mg once every 2 weeks is recommended

- for patients with a body weight of 50 kg or more, the recommended dose is 300 mg once every 4 weeks and, if additional LDL-C reduction is needed, a dose of 150 mg every 2 weeks is recommended

^*Of 3,115 very high-risk patients (including people with HeFH) and people with established CVD but without ACS or stroke, 979 had CAD or PAD + diabetes or established CAD.¹

^†PRALUENT is indicated in adults with established atherosclerotic cardiovascular disease to reduce cardiovascular risk by lowering LDL-C levels, as an adjunct to correction of other risk factors: in combination with the maximum tolerated dose of a statin with or without other lipid-lowering therapies or alone or in combination with other lipid-lowering therapies in patients who are statin-intolerant, or for whom a statin is contraindicated.⁵

^‡PAD + diabetes comprised patients with diabetes and a medical history of intermittent claudication together with ankle-brachial index ≤0.90, or together with peripheral revascularisation procedure/surgery, or critical limb ischaemia together with peripheral revascularisation procedure/surgery or thrombolysis. CAD + diabetes comprised patients with diabetes and a medical history of acute myocardial infarction, unstable angina, CAD, or coronary revascularisation. Clinically established CAD was defined as having a medical history of at least one of the following: angina pectoris, coronary angioplasty, coronary arterial stent insertion, coronary artery bypass, coronary artery surgery, coronary endarterectomy, coronary revascularisation, percutaneous coronary intervention.¹

^¥The subgroup PAD and diabetes was not analysed as a result of the small sample size (n=64).¹

ACS = acute coronary syndrome; Apo A1 = apolipoprotein Al; Apo B = apolipoprotein B; ASCVD = atherosclerotic cardiovascular disease; BMI = body mass index; CAD = coronary artery disease; CV = cardiovascular; CVD = cardiovascular disease; HbAlc = glycated haemoglobin; HDL-C = high-density lipoprotein cholesterol; HeFH = heterozygous familial hypercholesterolaemia; ITT = intention-to-treat; LDL-C = low-density lipoprotein cholesterol; Lp(a) = lipoprotein (a); LS = least squared; PAD = peripheral artery disease; PCSK9 = proprotein convertase subtilisin/kexin type 9; PCSK9i = proprotein convertase subtilisin/kexin type 9 inhibitor; Q2W = every 2 weeks; SAE = serious adverse event; SD = standard deviation; SE = standard error; TEA = treatment-emergent adverse event.