TY - JOUR
T1 - The Long-Term Efficacy and Safety of Evinacumab in Patients With Homozygous Familial Hypercholesterolemia
AU - Raal, Frederick J.
AU - Rosenson, Robert S.
AU - Reeskamp, Laurens F.
AU - Kastelein, John J.P.
AU - Rubba, Paolo
AU - Duell, P. Barton
AU - Koseki, Masahiro
AU - Stroes, Erik
AU - Ali, Shazia
AU - Banerjee, Poulabi
AU - Chan, Kuo Chen
AU - Khilla, Nagwa
AU - McGinniss, Jennifer
AU - Pordy, Robert
AU - Zhang, Yi
AU - Gaudet, Daniel
N1 - Funding Information: The authors thank the patients, their families, and all ELIPSE HoFH study investigators. Rinal Patel, PharmD, contributed to data acquisition. Medical writing support under direction of the authors was provided by Rebecca Mottram, PhD, and Atif Riaz, PhD, of Prime (Knutsford, United Kingdom), funded by Regeneron Pharmaceuticals, Inc, according to Good Publication Practice guidelines. The sponsors were involved in the study design, collection, analysis, and interpretation of data, as well as data checking of information provided in the manuscript. Publisher Copyright: © 2023 The Authors
PY - 2023/11
Y1 - 2023/11
N2 - Background: Homozygous familial hypercholesterolemia (HoFH) is characterized by early-onset atherosclerotic cardiovascular disease due to the high low-density lipoprotein cholesterol (LDL-C) burden. Patients with null-null low-density lipoprotein receptor (LDLR) variants respond poorly, if at all, to statins and proprotein convertase subtilisin/kexin type 9 inhibitors, which act by upregulating LDLR expression. The 24-week double-blind treatment period (DBTP) of the phase 3 ELIPSE HoFH (Evinacumab Lipid Studies in Patients with Homozygous Familial hypercholesterolemia; NCT03399786) study demonstrated significant LDL-C reductions in patients with HoFH; LDL-C reductions were also observed in those with null-null LDLR mutations. Objectives: The purpose of this study was to evaluate longer-term efficacy and safety of evinacumab in patients with HoFH from the ELIPSE HoFH study. Methods: Patients with HoFH on stable lipid-lowering therapies (LLTs) ± lipoprotein apheresis and screening LDL-C ≥70 mg/dL who completed the DBTP entered the 24-week open-label treatment period (OLTP) and received intravenous evinacumab 15 mg/kg every 4 weeks. OLTP results were summarized descriptively. Results: A total of 64 patients completed the DBTP and received open-label evinacumab. Despite multiple LLTs, the mean baseline LDL-C at DBTP entry was 250.5 ± 162.3 mg/dL. From baseline to week 48 (end of OLTP), evinacumab reduced mean LDL-C by 46.3% (mean reduction, 134.3 ± 117.3 mg/dL), with similar mean LDL-C reductions for patients with null-null (47.2%) and non-null variants (45.9%). Adverse events occurred in 47 (73.4%) patients; 4 (6.3%) patients experienced adverse events considered evinacumab-related (drug hypersensitivity, infusion-related reaction and asthenia, generalized pruritis, and muscle spasms). Conclusions: In patients with HoFH, evinacumab demonstrated substantial and sustained LDL-C reduction regardless of LDLR function, and was generally well tolerated.
AB - Background: Homozygous familial hypercholesterolemia (HoFH) is characterized by early-onset atherosclerotic cardiovascular disease due to the high low-density lipoprotein cholesterol (LDL-C) burden. Patients with null-null low-density lipoprotein receptor (LDLR) variants respond poorly, if at all, to statins and proprotein convertase subtilisin/kexin type 9 inhibitors, which act by upregulating LDLR expression. The 24-week double-blind treatment period (DBTP) of the phase 3 ELIPSE HoFH (Evinacumab Lipid Studies in Patients with Homozygous Familial hypercholesterolemia; NCT03399786) study demonstrated significant LDL-C reductions in patients with HoFH; LDL-C reductions were also observed in those with null-null LDLR mutations. Objectives: The purpose of this study was to evaluate longer-term efficacy and safety of evinacumab in patients with HoFH from the ELIPSE HoFH study. Methods: Patients with HoFH on stable lipid-lowering therapies (LLTs) ± lipoprotein apheresis and screening LDL-C ≥70 mg/dL who completed the DBTP entered the 24-week open-label treatment period (OLTP) and received intravenous evinacumab 15 mg/kg every 4 weeks. OLTP results were summarized descriptively. Results: A total of 64 patients completed the DBTP and received open-label evinacumab. Despite multiple LLTs, the mean baseline LDL-C at DBTP entry was 250.5 ± 162.3 mg/dL. From baseline to week 48 (end of OLTP), evinacumab reduced mean LDL-C by 46.3% (mean reduction, 134.3 ± 117.3 mg/dL), with similar mean LDL-C reductions for patients with null-null (47.2%) and non-null variants (45.9%). Adverse events occurred in 47 (73.4%) patients; 4 (6.3%) patients experienced adverse events considered evinacumab-related (drug hypersensitivity, infusion-related reaction and asthenia, generalized pruritis, and muscle spasms). Conclusions: In patients with HoFH, evinacumab demonstrated substantial and sustained LDL-C reduction regardless of LDLR function, and was generally well tolerated.
KW - angiopoietin-like protein 3
KW - clinical trial
KW - evinacumab
KW - homozygous familial hypercholesterolemia
KW - lipids
KW - lipoprotein
UR - http://www.scopus.com/inward/record.url?scp=85181706501&partnerID=8YFLogxK
U2 - https://doi.org/10.1016/j.jacadv.2023.100648
DO - https://doi.org/10.1016/j.jacadv.2023.100648
M3 - Article
SN - 2772-963X
VL - 2
JO - JACC: Advances
JF - JACC: Advances
IS - 9
M1 - 100648
ER -