PCSK9 antibody therapy leads to effective and sustained LDL-c and Lp(a) decrease
Effect of Alirocumab on Lipoprotein(a) Over ≥1.5 Years (from the Phase 3 ODYSSEY Program)
Gaudet D, Watts GF, Robinson JG, et al.
Am J Cardiol 2016; published online ahead of print
BackgroundIn ten phase 3 ODYSSEY studies, alirocumab, a monoclonal antibody against PCSK9, was able to reduce LDL-c levels from baseline to up to 62% during 24 weeks. These studies predominantly involved patients at high CV risk [1,2]. According to a pooled analysis of three alirocumab phase 2 studies, the median Lp(a) reduction was 30% after 8 to 12 weeks of treatment, and in individual phase 3 studies, alirocumab reduced Lp(a) by an average of 25% to 30% within 24 weeks [3-5].
In this pooled analysis of ten phase 3 studies (LONG TERM, HIGH FH, COMBO I, FH I, FH II, COMBO II, OPTIONS I, OPTIONS II, ALTERNATIVE, MONO), the maintenance of the Lp(a)-lowering effect with alirocumab over 24 to 104 weeks was assessed in 4,915 participants.
- Reductions in Lp(a) were maintained up to end of study in the 78-week study and 104-week study.
- Among patients with baseline Lp(a) ≥50 to <75 mg/dL, 47.1% to 61.7% of alirocumab-treated patients achieved Lp(a) <50 mg/dL by week 24.
- In patients with HeFH from the FH I and FH II trials, Lp(a) was reduced by 26.9% within 24 weeks with alirocumab 75/150 mg every 2 weeks versus 8.5% with placebo (mean difference -18.4%; P<0.0001).
- In patients with HeFH from the LONG TERM and HIGH FH trials, Lp(a) decreased by 26.0% at week 24 in the alirocumab 150 mg every 2 weeks group and by 2.8% in the placebo group (mean difference -23.3%; P<0.0001).
- Greater percentage reductions in Lp(a) showed a moderate-to-low correlation with greater percentage reductions in LDL-c (Spearman’s correlation coefficient: 0.307). A moderate-to-low correlation between percentage reduction in Lp(a) versus LDL-c was also observed when patient groups with baseline Lp(a) <50 or ≥50 mg/dL as well as with and without HeFH were analysed separately.
- Overall rates of treatment-emergent adverse events in the trials included in this analysis were similar between alirocumab and control patients.
ConclusionThe consistent reductions in Lp(a) observed across the studies suggest that PCSK9 inhibition with alirocumab not only effectively lowers LDL-c but also has a substantial, sustained effect on Lp(a).
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