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. 2022 Nov 11;15(11):1389.
doi: 10.3390/ph15111389.

Long-Term Efficacy and Safety of Evinacumab in Patients with Homozygous Familial Hypercholesterolemia: Real-World Clinical Experience

Claudia Stefanutti  1 , Dick C Chan  2 , Serafina Di Giacomo  1 , Claudia Morozzi  1 , Gerald F Watts  2   3
Affiliations

Long-Term Efficacy and Safety of Evinacumab in Patients with Homozygous Familial Hypercholesterolemia: Real-World Clinical Experience

Claudia Stefanutti et al. Pharmaceuticals (Basel). .

Abstract

Homozygous familial hypercholesterolemia (HoFH) is a rare, genetic condition characterized by markedly elevated plasma low-density lipoprotein cholesterol (LDL-C) concentrations from birth and increased risk of premature atherosclerotic cardiovascular disease. Evinacumab is an inhibitor of angiopoietin-like 3 protein that offers a new approach for correcting high LDL-C in HoFH. Evinacumab was administered intravenously (15 mg/kg Q4W) for 24 months in 7 patients with genetically confirmed HoFH, receiving background lipoprotein apheresis (LA) and/or lipid-lowering treatment (LLT). Assessment of efficacy and safety were carried out before and after 24 months of evinacumab treatment. The LDL-C lowering effect of evinacumab without LA were also investigated in the 7 HoFH patients after a subsequent compassionate extension period. Twenty-four months of treatment with evinacumab against background LA and LLT resulted in a significant reduction in LDL-C (−46.8%; p < 0.001). LDL-C reduction with evinacumab was maintained during the compassionate extensions period in the absence of treatment with LA (−43.4%; mean follow-up of 208 ± 90 days). Evinacumab was well-tolerated, with no major adverse event reported or significant changes in liver and muscle enzyme concentrations. Our findings suggest that evinacumab is a safe and effective treatment for patients with HoFH receiving best standard of care in a routine setting.

Keywords: angiopoietin-like 3 protein inhibitors; atherosclerotic cardiovascular disease; familial hypercholesterolemia; lipoprotein apheresis; low-density lipoprotein.

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Conflict of interest statement

CS has received honoraria for consultancy and speaking engagements from Aegerion, Fresenius Medical Care and Kaneka NV. GFW has received honoraria for advisory boards and research grants from Amgen, Arrowhead, Esperion, AstraZeneca, Kowa, Novartis, Pfizer, Sanofi and Regeneron. DC, SDG and CM declare no conflict of interest.

Figures

Figure 1
Figure 1
Change in plasma LDL-C concentration during 24-month treatment with evinacumab and LA in HoFH patients; individual (A) and mean (B) responses of patients. Mean ± SEM * p < 0.001 compared to baseline. No significant difference in plasma LDL-C concentration at 6, 12, 18 and 24 months.
Figure 1
Figure 1
Change in plasma LDL-C concentration during 24-month treatment with evinacumab and LA in HoFH patients; individual (A) and mean (B) responses of patients. Mean ± SEM * p < 0.001 compared to baseline. No significant difference in plasma LDL-C concentration at 6, 12, 18 and 24 months.
Figure 2
Figure 2
Percentage change from baseline in LDLC at 24-month follow-up (evinacumab plus LA) and during the compassionate extension phase follow-up (evinacumab alone) for individual patients. * Patient 6 received evinacumab treatment only during 24-month follow-up and the compassionate extension phase.
Figure 3
Figure 3
Change from baseline in TC (A), non-HDL-C (B) and apoB (C) during 24-month treatment with evinacumab and LA. Mean ± SEM. * p < 0.001 compared to baseline; No significant difference in plasma TC, non-HDL-C and apoB concentrations at 6, 12, 18 and 24 months.
Figure 4
Figure 4
Percentage change from baseline in total cholesterol (A), non-HDL-cholesterol (B) and apoB (C) at 24-month follow-up for individual patients.
Figure 5
Figure 5
Percentage change from baseline in TG (A), HDL-C (B), REM-C (C), apoA-I (D), apoC-III (E) and Lp(a) (F) at 24-month follow-up for individual patient. Baseline apoC-III data were not available in 2 HoFH (patients 2 and 7).
Figure 6
Figure 6
Change from baseline in plasma aspartate transaminase (A), alanine transaminase (B) and creatine kinase (C) during 24-month treatment with evinacumab. Dotted lines represent upper limit of normal (ULN) and 3X ULN for aspartate transaminase (AST), alanine transaminase (ALT) and creatine kinase (CK).
Figure 7
Figure 7
Consort diagram for the study.
See this image and copyright information in PMC

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