Efficacy and Safety of Alirocumab in Patients with Heterozygous Familial Hypercholesterolemia and LDL-C of 160 mg/dl or Higher

PURPOSE: Even with statins and other lipid-lowering therapy (LLT), many patients with heterozygous familial hypercholesterolemia (heFH) continue to have elevated low-density lipoprotein cholesterol (LDL-C) levels. ODYSSEY HIGH FH (NCT01617655) assessed the efficacy and safety of alirocumab, a proprotein convertase subtilisin/kexin type 9 monoclonal antibody, versus placebo in patients with heFH and LDL-C ≥ 160 mg/dl despite maximally tolerated statin ± other LLT. METHODS: Patients were randomized to subcutaneous alirocumab 150 mg or placebo every 2 weeks (Q2W) for 78 weeks. The primary endpoint was percent change in LDL-C from baseline to week 24. RESULTS: Mean baseline LDL-C levels were 196.3 mg/dl in the alirocumab (n = 71) and 201.0 mg/dl in the placebo groups (n = 35). Significant mean (standard error [SE]) reductions in LDL-C from baseline to week 24 were observed with alirocumab (-45.7 [3.5] %) versus placebo (-6.6 [4.9] %), a difference of -39.1 (6.0) % (P < 0.0001). Absolute mean (SE) LDL-C levels were reduced from baseline by 90.8 (6.7) mg/dl with alirocumab at week 24, with reductions maintained to week 78. Treatment-emergent adverse events were generally comparable between groups. Injection-site reactions were more frequent in the alirocumab group (8.3 %) versus placebo (5.7 %); most were mild in severity and did not result in study medication discontinuation. CONCLUSIONS: In patients with heFH and very high LDL-C baseline levels despite maximally tolerated statin ± other LLT, alirocumab 150 mg Q2W demonstrated significant reductions in LDL-C levels with 41 % of patients achieving predefined LDL-C goals. Alirocumab was generally well tolerated.