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

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• 作者：Robert Dufour^a ; ^{robert.dufour@ircm.qc.ca} ; Jean Bergeron^b ; Daniel Gaudet^c ; Robert Weiss^d ; G. Kees Hovingh^e ; Zhizhi Qing^f ; Feng Yang^g ; Matthew Andisik^g ; Albert Torri^g ; Robert Pordy^g ; Daniel A. Gipe^g
• 关键词：AE ; adverse event ; Apo ; apolipoprotein ; CVD ; cardiovascular disease ; HDL-C ; high-density lipoprotein cholesterol ; HeFH ; heterozygous familial hypercholesterolemia ; LDL-C ; low-density lipoprotein cholesterol ; Lp(a) ; lipoprotein (a) ; LLT ; lipid-lowering therapy ; MedDRA ; Medical Dictionary for Regulatory Activities ; MI ; myocardial infarction ; PCSK9 ; proprotein convertase subtilisin/kexin type 9 ; Q2W ; every 2  ; weeks ; Q4W ; every 4  ; weeks ; SD ; standard deviation ; TEAE ; treatment-emergent adver
• 刊名：International Journal of Cardiology
• 出版年：2017
• 出版时间：1 February 2017
• 年：2017
• 卷：228
• 期：Complete
• 页码：754-760
• 全文大小：759 K
• 卷排序：228

文摘

PCSK9 inhibition with alirocumab significantly reduced LDL-C levels in trials of up to 78 weeks' duration in patients with heterozygous familial hypercholesterolemia (HeFH). We report results from 3 years of an ongoing open-label treatment extension (NCT01576484) to a 12-week double-blind trial in HeFH patients (NCT01266876).MethodsPatients who completed the parent study and were receiving stable daily statin ± ezetimibe could enter the open-label extension, where they received alirocumab 150 mg 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.ResultsMean baseline LDL-C was 150.7 mg/dL (3.9 mmol/L), despite all patients being on a statin (76% on high-intensity statin; 72% also receiving ezetimibe). Over 156 weeks, 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 148 weeks (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).ConclusionsOpen-label treatment for 3 years with alirocumab 150 mg 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.