Relationship between alirocumab, PCSK9, and LDL-C levels in four phase 3 ODYSSEY trials using 75 and 150 mg doses

Jennifer G Robinson, Michel Farnier, John J P Kastelein, Eli M Roth, Marja-Riitta Taskinen, Helen M Colhoun, Aurelie Brunet, A Thomas DiCioccio, Guillaume Lecorps, Robert Pordy, Marie T Baccara-Dinet, Christopher P Cannon

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

BACKGROUND: Alirocumab is a monoclonal antibody to proprotein convertase subtilisin/kexin type 9 (PCSK9).

OBJECTIVE: Changes in PCSK9, alirocumab, and low-density lipoprotein cholesterol (LDL-C) levels were assessed after treatment with alirocumab at doses of 75 or 150 mg every 2 weeks (Q2W).

METHODS: Data were analyzed from 4 phase 3 trials (MONO; COMBO II; FH I; LONG TERM); all but MONO enrolled patients on statins. Three trials evaluated alirocumab 75 mg Q2W, with possible dose increase to 150 mg Q2W at week 12 based on week 8 LDL-C; LONG TERM studied alirocumab 150 mg Q2W.

RESULTS: Patients on background statin therapy had higher mean baseline free PCSK9 concentrations vs patients not on statin. After alirocumab administration, increased alirocumab concentrations were associated with dramatic reductions in circulating free PCSK9, resulting in significant LDL-C reductions and a corresponding increase in inactive PCSK9:alirocumab complex. Alirocumab dose increase was associated with a further lowering of PCSK9 and LDL-C. Patients with higher baseline LDL-C levels (>160 mg/dL) were more likely to have their dose increased. LDL-C reductions with alirocumab were consistent between patients with baseline PCSK9 levels above or below the median when the dose increase strategy was used. When started as alirocumab 150 mg Q2W, patients with PCSK9 levels above vs below the median had a greater LDL-C reduction.

CONCLUSIONS: Alirocumab-induced changes in PCSK9 and LDL-C levels were consistent with the known physiologic relationship between PCSK9, LDL receptor, and LDL-C levels, as well as statin-induced increases in PCSK9 production.

Original languageEnglish
Pages (from-to)979-988.e10
JournalJournal of clinical lipidology
Issue number6
Early online date14 Oct 2019
Publication statusPublished - 12 Nov 2019


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