To evaluate the overall durability of the effect of alirocumab in patients with heterozygous familial hypercholesterolemia (HeFH) using data from the ODYSSEY open-label extension (OLE) of four phase 3 trials (FHI, FHII, LONG-TERM, HIGH-FH) assessing long-term efficacy and safety for up to 40 months.

Patients received alirocumab 75mg (FHI, FHII, LONG-TERM) or 150mg (HIGH-FH) once every 2 weeks. From Week 12, dose adjustment of alirocumab was allowed as per investigator's clinical judgement.

A total of 985 patients (mean age 54.4 years, 55.8% male) were included in OLE safety population. At OLE enrollment, 978 patients were receiving statins with 627 other lipid-lowering therapy. At the time of analysis, 938 patients had completed≥1 year of treatment; 5.7% had discontinued treatment (2.2% due to adverse events). Of those who started OLE on 75mg dose, 537/909 (59.1%) were maintained on that dose throughout. At Week 48 of OLE, the mean LDL-C was 79.7mg/dL, a mean reduction of 46.9% compared with baseline levels of the parent studies. Other lipid changes included reductions at Week 48 in non-high density lipoprotein cholesterol (40.3%), total cholesterol (29.7%), lipoprotein(a) (25.6%), and apolipoprotein B (37.5%). Overall, 762/985 (77.4%) patients reported treatment-emergent adverse events during OLE (up to 73 weeks). Injection site reactions reported by 49 patients (5.0%) were mild and self-limited.

In this OLE study of patients with HeFH, alirocumab demonstrated a durable and robust treatment effect, yielding a 47% reduction in LDL-C at Week 48 compared with baseline levels.