Alirocumab efficacy and safety by race and ethnicity: Analysis from 3 ODYSSEY phase 3 trials

Abstract

BACKGROUND: Differences in lipid and cardiovascular risk profiles have been observed in African-American/black (AA/B), white (W), and Hispanic/Latino (H/L) individuals. Efficacy and safety of alirocumab, a proprotein convertase subtilisin/kexin type 9 inhibitor, may vary by race and ethnicity and has not been analyzed. OBJECTIVE: This post hoc analysis evaluated alirocumab efficacy and safety vs control in 3 pooled ODYSSEY phase 3 trials (COMBO I, COMBO II, and LONG TERM) by race (AA/B [n 5 154] vs W [n 5 1982]) and ethnicity (H/L [n 5 174] vs non-H/L [n 5 3149]). METHODS: Patients with elevated low-density lipoprotein cholesterol (LDL-C) despite maximally tolerated statin received alirocumab (75 mg up to 150 mg every 2 weeks [COMBO I & II] or 150 mg every 2 weeks [LONG TERM]) or control (placebo [COMBO I and LONG TERM] or ezetimibe [COMBO II]). RESULTS: At baseline, LDL-C levels were similar across treatment groups; median lipoprotein(a) levels were higher in AA/B (33.0-120.0 mg/dL) vs W (7.1-66.3 mg/dL) and lower in H/L (5.0-38.3 mg/dL) vs non-H/L (7.7-69.0 mg/dL). At week 24, alirocumab significantly reduced LDL-C vs control. Alirocumab also reduced lipoprotein(a) compared with control across the subgroups. Treatment-emergent adverse events were similar between alirocumab (68.9-85.0%) and control (70.6-82.4%) regardless of race and ethnicity. CONCLUSION: Alirocumab significantly reduced LDL-C and Lp(a) levels compared with control, regardless of race and ethnicity, with overall safety comparable to control across most of the racial and ethnic groups analyzed.

Familial hypercholesterolemia in Southeast and East Asia

“…In the ODYSSEY FH I and FH II trials of predominantly white heterozygous FH patients, alirocumab was associated with a similar (51–59%) reduction in LDL-C [69] . In post-hoc analyses evaluating the efficacy of alirocumab in three ODYSSEY phase 3 trials, reductions in LDL-C were comparable regardless of race/ethnicity (White 58.7%; Black 42.9%; Hispanic/Latino 50.6%) [70] . Furthermore, the pharmacokinetic and pharmacodynamic characteristics of PCSK9 inhibitors appear to be similar between White and Asian (Japanese and Chinese) populations [71] .…”

PCSK9 in African Americans and Caucasians in Relation to Lp(a) Level, Apo(a) Size and Heritability

“…While PCSK9 levels were somewhat higher in African Americans vs Caucasians, particularly among adults, the PCSK9/Lp(a) ratio differed considerably; although any effect of PCSK9 inhibitors has not been shown to differ across ethnicity [ 31 ]. An increase in apo(a) fractional catabolic rate (~25%) and a modest decrease in apo(a) production rate (~9%) has been reported during treatment with PCSK9 inhibitors [ 32 ].…”

Lipoprotein(a) and PCSK9 inhibition: clinical evidence

“… 12 These effects were regardless of race and ethnicity with a mean reduction from baseline of −28.3% in White, −20.4% in African-American/Black, −25,7% in Hispanic/Latinos, and −28.4% in non-Hispanic/Latinos. 13 …”