Long-term safety and efficacy of alirocumab in patients with heterozygous familial hypercholesterolemia: An open-label extension of the ODYSSEY program

Background and aims: ODYSSEY OLE (open-label extension; NCT01954394) included patients diagnosed with heterozygous familial hypercholesterolemia (HeFH), receiving maximally tolerated statins, who had completed one of four Phase 3 double-blind parent studies (all 18 months' duration), with the aim to assess longer-term safety and efficacy of alirocumab. Methods: Patients received starting dose alirocumab 75 mg every 2 weeks (Q2W; patients from FH I, FH II, and LONG TERM) or alirocumab 150 mg Q2W (patients from HIGH FH). Low-density lipoprotein cholesterol (LDL-C) levels were blinded to the patient and physician until Week 8; from Week 8, LDL-C levels were communicated to physicians. From Week 12, dose adjustment from 75 to 150 mg Q2W, or vice versa, was possible per physician's clinical judgment according to patient's LDL-C levels. Results: Patients who had received alirocumab (n = 655) compared with placebo (n = 330) in the parent studies exhibited similar rates of treatment-emergent adverse events (TEAEs; 87.3% vs. 83.9%) during OLE (2.5 years median alirocumab exposure). Overall, 33 patients (3.4%) experienced TEAEs leading to permanent treatment discontinuation. At Week 8, alirocumab reduced mean LDL-C by 44.2% (reduction from 151.9 mg/dL at parent study baseline to 84.9 mg/dL); reduction in LDL-C was consistent to Week 96 of OLE. Reductions in lipid parameters were similar regardless of treatment allocation in the parent study. Conclusions: In patients with HeFH, no unexpected long-term safety concerns were observed with alirocumab compared with previously published data; durability of LDL-C-lowering over 3 years (including 1.5 years of parent trials) was demonstrated.