Efficacy and safety of alirocumab in Korean patients with hypercholesterolemia and high cardiovascular risk: subanalysis of the ODYSSEY-KT study

Abstract

Background/aims: Efficacy and safety data of alirocumab, a fully human monoclonal antibody to proprotein convertase subtilisin/kexin type 9 (PCSK9), is not yet well established in the Korean population. We assessed them in ODYSSEY-KT through the pre-specified Korean subanalysis.

Methods: In the ODYSSEY-KT study, South Korean and Taiwanese patients with hypercholesterolemia and high cardiovascular risks were randomized (1:1) to alirocumab or placebo. Alirocumab was self-administered subcutaneously at 75 mg every 2 weeks with a maximally tolerated statin dose with or without other lipid-modifying therapies. Alirocumab dose was increased to 150 mg every 2 weeks at week 12 if low density lipoprotein cholesterol (LDL-C) ≥ 70 mg/dL at week 8. Primary endpoint was percent change in LDL-C from baseline to week 24. Results from Korean cohort (n = 83: 40 for alirocumab and 43 for placebo, respectively) analyses are reported here.

Results: In alirocumab group, the least square of mean change percent in LDL-C levels was -65.7% (placebo: 11.1%; p < 0.0001) and 92.0% of them achieved LDL-C < 70 mg/dL (placebo: 12.7%; p < 0.0001) at week 24. Alirocumab also showed significantly greater improvements in high density lipoprotein cholesterol (HDL-C), non-HDL-C, total cholesterol, lipoprotein(a), and apolipoprotein B than placebo (p < 0.05). Two consecutive calculated LDL-C values < 25 mg/dL were observed in 37.5% of alirocumab-treated patients. Overall, 45.0% alirocumab-treated and 51.2% placebo-treated patients experienced treatment-emergent adverse events (TEAEs) without discontinuation of treatment due to TEAEs.

Conclusion: Alirocumab has demonstrated to be effective in improvement of LDL-C and related lipid profiles in Korean cohort. Alirocumab was generally well tolerated with no significant safety signals.

Keywords: Cholesterol, LDL; Hypercholesterolemia; ODYSSEY; PCSK9.

Figure 1.

Patient flow: CONSORT diagram. ITT, intent-to-treat; mITT, modified intent-to-treat.

Figure 2.

Calculated low density lipoprotein cholesterol levels (least-squares mean ± standard error) in intent-to-treat population during treatment phase. q2w, every 2 weeks.

Figure 3.

Least squares mean difference (vs. placebo) in low density lipoprotein cholesterol (LDL-C) and secondary lipid parameters in patients in the alirocumab group in intentto-treat population. LDL-C levels given were calculated values. Triglyceride levels were ascertained under fasting conditions. HDL-C, high density lipoprotein cholesterol; TG, triglyceride; TC, total cholesterol; Lp(a), lipoprotein(a); Apo A1, apolipoprotein A1; Apo B, apolipoprotein B.

Figure 4.

Least squares mean difference (vs. placebo) in low density lipoprotein cholesterol (LDL-C) and secondary lipid parameters in patients in the alirocumab group in modified intent-to-treat population. LDL-C levels given were calculated values. Triglyceride levels were ascertained under fasting conditions. HDL-C, high density lipoprotein cholesterol; TG, triglyceride; TC, total cholesterol; Lp(a), lipoprotein(a); Apo A1, apolipoprotein A1; Apo B, apolipoprotein B.