ON-TREATMENT LDL-C LEVELS WHEN ALIROCUMAB DOSE IS DECREASED FROM 150 TO 75 MG EVERY 2 WEEKS IN PATIENTS WITH HETEROZYGOUS FAMILIAL HYPERCHOLESTEROLEMIA: RESULTS FROM ODYSSEY

Abstract

Alirocumab (ALI) is available in two doses, 75 and 150 mg (to be administered once every 2 weeks [Q2W]). ODYSSEY LONG TERM was a 78-week double-blind trial of ALI 150 mg Q2W versus placebo, as add-on to maximally tolerated statin ± other lipid-lowering therapy (LLT). Patients with heterozygous familial hypercholesterolemia (HeFH) who completed LONG TERM could enter the open-label ODYSSEY OLE (NCT01954394) following an 8-week off-drug wash out period. From the start of OLE up to Week 8, all patients received ALI 75 mg Q2W (with their existing statin/other LLT). For the first time, this gives the opportunity to assess on-treatment LDL-C levels when the dose of ALI is decreased from 150 to 75 mg Q2W in a cohort of HeFH patients. On-treatment LDL-C levels and % change from baseline were compared in the same cohort of patients at Week 8 of LONG TERM (when all patients received ALI 150 mg Q2W) versus Week 8 in OLE (when all received ALI 75 mg Q2W). Baseline and efficacy data were assessed in an on-treatment (mITT) analysis. Safety in OLE was assessed up to the cut-off date for this analysis. A total of 214 patients with HeFH who completed LONG TERM entered OLE (mITT population n=211). Mean (SD) LDL-C of this cohort of patients in LONG TERM was 162.3 (58.6) mg/dL at baseline and 61.6 (42.9) mg/dL at Week 8 with ALI 150 mg (63.1% reduction). For the same cohort of patients in OLE (following 78 weeks of LONG TERM study plus 8 weeks wash-out), mean (SD) LDL-C was 166.6 (59.5) mg/dL at baseline and 89.6 (54.9) mg/dL at Week 8 with ALI 75 mg (47.3% reduction). Safety data for this cohort from OLE were available for ∼12 months: 76.6% reported a treatment-emergent adverse event (TEAE) and 1.4% discontinued due to a TEAE. Local injection site reactions were reported by 4.7%, neurological TEAEs by 3.3%, neurocognitive TEAEs by 0.9%, and hepatic disorders by 1.9% of patients, consistent with what was observed in the 18-month double-blind parent trial. In the same cohort of patients with HeFH receiving statin ± other LLT, absolute LDL-C reductions were 77.0 mg/dL with ALI 75mg Q2W, and 100.7 mg/dL with ALI 150 mg Q2W.