Individualized low-density lipoprotein cholesterol reduction with alirocumab titration strategy in heterozygous familial hypercholesterolemia: Results from an open-label extension of the ODYSSEY LONG TERM trial.

Background: Patients with heterozygous familial hypercholesterolemia (HeFH) who completed the double-blind ODYSSEY LONG TERM parent trial and subsequently enrolled in the open-label extension (OLE) study, ODYSSEY OLE (NCT01954394), provide a unique opportunity to investigate effects of 2 doses of alirocumab, a proprotein convertase subtilisin/kexin type 9 inhibitor, within the same patient cohort.

Objective: The aim of the study was to characterize long-term efficacy and safety of 2 alirocumab dosages and utility of a dose titration strategy in patients with HeFH.

Methods: After an 8-week washout period, patients with HeFH who completed the LONG TERM study (receiving alirocumab 150 mg every 2 weeks [Q2W]) were eligible to enroll in OLE (n = 214) for up to 40 months' treatment duration. In OLE, patients started on alirocumab 75 mg Q2W. From Week 12, dose adjustment from 75 to 150 mg Q2W or vice versa was possible based on physician's clinical judgment.

Results: During the LONG TERM trial, alirocumab 150 mg Q2W reduced mean low-density lipoprotein cholesterol (LDL-C) from baseline (162.3 mg/dL) to Week 8 by 63.1%; during OLE, alirocumab 75 mg Q2W reduced mean LDL-C from baseline (166.6 mg/dL) by 47.3% within the same patient cohort. At Week 96, mean LDL-C reduction from OLE baseline was 55.4% vs 46.8% for patients with or without alirocumab dose increase, respectively. Treatment-emergent adverse events leading to permanent treatment discontinuation were observed in 4 patients (1.9%).

Conclusions: In patients with HeFH, both alirocumab dosages provided consistent LDL-C reductions over a treatment duration of up to 4 years (including 1.5 years of the LONG TERM trial), allowing an individualized approach to LDL-C lowering, depending on baseline LDL-C levels.