PRALUENT LONG-TERM STUDY

The usual starting dose for praluent is 75mg administered subcutaneously once every 2 weeks. Patients requiring larger LDL-C reduction (>60%) may be started on 150mg once every 2 weeks.

Efficacy and Safety of Alirocumab in Reducing Lipids*

Robinson J.G, et al. N Engl J Med 2015; 372:1489–99.

*All of the information and data within this section (unless noted) is a summary of this publication.

Study objectives

The ODYSSEY LONG TERM study evaluated the long term efficacy and safety of Praluent 150mg versus placebo as an add-on to maximally tolerated dose (MTD) statin** ± other lipid-lowering therapy (LLT) in high cardiovascular (CV) risk patients with inadequately controlled hypercholesterolaemia.

Study design

This 78 week, multicentre, randomised, double-blind, placebo-controlled, parallel group, phase III study involved 2,341 adult patients (≥18 years) with heterozygous familial hypercholesterolaemia (HeFH) (as determined by genotyping or clinical criteria) or established coronary heart disease (CHD) or CHD risk equivalent†, a LDL-C level ≥1.8 mmol/L and all patients were receiving MTD statins* ± other LLTs.

Patients were randomised to subcutaneous Praluent 150 mg every 2 weeks (Q2W) (n=1,553) or placebo Q2W (n=788) (Figure 1).

The primary efficacy endpoint was the percentage change in LDL-C from baseline to Week 24. Secondary endpoints included:

Proportion of patients achieving the pre-specified LDL-C level target of ≤1.8 mmol/L at Week 24
Percentage change in LDL-C from baseline to Week 78
Safety profile including incidence of treatment-emergent adverse events (TEAEs), treatment-emergent serious AEs (SAEs), injection site reactions and adjudicated CV events.

Figure 1: ODYSSEY LONG TERM: Study design - Adapted from Robinson J.G, et al. N Engl J Med 2015; 372:1489–99¹

Baseline Characteristics

Baseline characteristics were well balanced between the treatment groups (Table 1).

Table 1: ODYSSEY LONG TERM: Baseline characteristics - Adapted from Robinson J.G, et al. N Engl J Med 2015; 372:1489–99¹

Key efficacy results

In high CV risk patients with inadequately controlled hypercholesterolaemia, Praluent 150mg Q2W led to significantly greater reductions in LDL-C compared to placebo (Figure 2), allowed a significantly greater proportion of patients to achieve the pre-specified LDL-C target compared to placebo and the LDL-C reductions were consistent and sustained over 78 weeks (Figure 4):

• At Week 24, mean percentage change in LDL-C from baseline was -61.0% (1.93mmol/L) for Praluent versus +0.8% (0.8mmol/L) for placebo (p<0.001)
• At Week 24, 79.3% of Praluent versus 8% of placebo patients achieved the pre-specified LDL-C target of ≤1.8 mmol/L (p<0.001)
• At Week 78, mean percentage change in LDL-C from baseline was -52.4% (0.1mmol/L) for Praluent versus +3.6% (1.66mmol/L) for placebo (p<0.001)* and a consistent reduction in LDL-C level from baseline was observed from Week 4 to Week 78 in the Praluent group (Figure 4).

*This P value was not adjusted for multiplicity and is descriptive only.

Figure 2: ODYSSEY LONG TERM: Mean reduction in LDL-C from baseline to Week 24 - Adapted from Robinson J.G, et al. N Engl J Med 2015; 372:1489–991

Figure 3: ODYSSEY LONG TERM: Mean reduction in LDL-C from baseline to Week 24 by baseline LDL-C2 - Adapted from Robinson JG, et al. N Engl J Med 2015;372(16):Suppl.

Figure 4: ODYSSEY LONG TERM: Mean reduction in LDL-C from baseline to Week 78 - Adapted from Robinson JG, et al. N Engl J Med 2015;372(16):1489-99

Key safety results

2,338 patients, 1,550 patients for Praluent and 788 for placebo, were included in the safety analysis.

• Mean duration of follow-up - 80.9 weeks for Praluent and 80.1 weeks for placebo.
• Mean study-drug exposure was 70 weeks, providing 2,061 patient-years of exposure to Praluent 150mg Q2W.

Frequency of any AEs and SAEs were comparable in Praluent and placebo patients (Table 2). Although compared with placebo, Praluent had higher rates of AEs leading to discontinuation, injection site reactions, myalgia, neurocognitive disorders and ophthalmologic events (Table 2), with the exception of myalgia, these differences were not statistically significant.

The number of cardiovascular events was relatively small, which limits the robustness of these data and the confidence that they are not simply a chance finding.

A post hoc analysis was performed that compared the rate of positively adjudicated major adverse cardiovascular events between the two study groups, using the composite end point of death from coronary heart disease, nonfatal myocardial infarction, fatal or nonfatal ischemic stroke, or unstable angina requiring hospitalisation.

Table 2: ODYSSEY LONG TERM: Adverse events (safety population) - Adapted from Robinson J.G, et al. N Engl J Med 2015; 372:1489–991

^*These P values were not adjusted for multiplicity and are descriptive only.

Please refer to publication for full safety profile information
CHD = coronary heart disease; CV = cardiovascular

Conclusions

• Praluent 150 mg every two weeks achieved significantly lowered LDL-C from baseline to Week 24 in patients with high CV risk patients on the maximally tolerated dose of statin therapy in comparison to placebo (-61.0% (1.93mmol/L) for Praluent versus +0.8% (0.8mmol/L) for placebo; p<0.001);
• Praluent demonstrated sustained long-term LDL-C lowering in comparison to placebo from week 4 to week 78 (-52.4% (0.1mmol/L) for Praluent versus +3.6% (1.66mmol/L) for placebo);
• Praluent 150 mg every two weeks demonstrated significant LDL-C lowering compared to placebo regardless of baseline LDL-C (interaction p<0.0001)2;
• The incidences of TAEAs and serious TEAEs were comparable between treatment groups.