Open-label therapy with alirocumab in patients with heterozygous familial hypercholesterolemia: Results from three years of treatment.

Background: PCSK9 inhibition with alirocumab significantly reduced LDL-C levels in trials of up to 78weeks' duration in patients with heterozygous familial hypercholesterolemia (HeFH). We report results from 3years of an ongoing open-label treatment extension (NCT01576484) to a 12-week double-blind trial in HeFH patients (NCT01266876).

Methods: Patients who completed the parent study and were receiving stable daily statin±ezetimibe could enter the open-label extension, where they received alirocumab 150mg every 2 weeks (Q2W) subcutaneously (n=58). The primary endpoint was safety (treatment-emergent adverse events, TEAEs). Efficacy endpoints included the percentage change in LDL-C from baseline at Week 24. Safety and efficacy data were available up to Weeks 156 and 148, respectively.

Results: Mean baseline LDL-C was 150.7mg/dL (3.9mmol/L), despite all patients being on a statin (76% on high-intensity statin; 72% also receiving ezetimibe). Over 156weeks, 54 (93.1%) patients experienced a TEAE, 12 (20.7%) experienced a serious TEAE, and two (3.4%) discontinued due to a TEAE. Injection site reactions occurred in 21 (36.2%) patients. Mean (SD) reduction in LDL-C from baseline to Week 24 was 65.4 (21.1)%, with reductions maintained through 148weeks (Week 148 reduction: 56.0 [23.8]%). Mean apolipoprotein B reduction was 50.9% and median lipoprotein (a) reduction was 22.5% at Week 24 (46.1% and 25.6% at Week 148, respectively).

Conclusions: Open-label treatment for 3years with alirocumab 150mg Q2W, administered with background statin±ezetimibe, was generally well-tolerated and had a safety profile comparable with that seen in the overall alirocumab clinical trial program. Alirocumab provided significant, sustained LDL-C reductions.