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Clinical Trial
. 2024 Jul 12;45(27):2422-2434.
doi: 10.1093/eurheartj/ehae325.

Evinacumab in homozygous familial hypercholesterolaemia: long-term safety and efficacy

Daniel Gaudet  1 , Susanne Greber-Platzer  2 , Laurens F Reeskamp  3 , Gabriella Iannuzzo  4 , Robert S Rosenson  5 , Samir Saheb  6 , Claudia Stefanutti  7 , Erik Stroes  3 , Albert Wiegman  8 , Traci Turner  9 , Shazia Ali  10 , Poulabi Banerjee  10 , Tiera Drewery  10 , Jennifer McGinniss  10 , Alpana Waldron  10 , Richard T George  10 , Xue-Qiao Zhao  10 , Robert Pordy  10 , Jian Zhao  10 , Eric Bruckert  11 , Frederick J Raal  12
Affiliations
Clinical Trial

Evinacumab in homozygous familial hypercholesterolaemia: long-term safety and efficacy

Daniel Gaudet et al. Eur Heart J. .

Erratum in

Abstract

Background and aims: Homozygous familial hypercholesterolaemia (HoFH) is a rare genetic disorder characterized by severely elevated LDL cholesterol (LDL-C) and premature atherosclerotic cardiovascular disease. In the pivotal Phase 3 HoFH trial (NCT03399786), evinacumab significantly decreased LDL-C in patients with HoFH. This study assesses the long-term safety and efficacy of evinacumab in adult and adolescent patients with HoFH.

Methods: In this open-label, single-arm, Phase 3 trial (NCT03409744), patients aged ≥12 years with HoFH who were evinacumab-naïve or had previously received evinacumab in other trials (evinacumab-continue) received intravenous evinacumab 15 mg/kg every 4 weeks with stable lipid-lowering therapy.

Results: A total of 116 patients (adults: n = 102; adolescents: n = 14) were enrolled, of whom 57 (49.1%) were female. Patients were treated for a median (range) duration of 104.3 (28.3-196.3) weeks. Overall, treatment-emergent adverse events (TEAEs) and serious TEAEs were reported in 93 (80.2%) and 27 (23.3%) patients, respectively. Two (1.7%) deaths were reported (neither was considered related to evinacumab). Three (2.6%) patients discontinued due to TEAEs (none were considered related to evinacumab). From baseline to Week 24, evinacumab decreased mean LDL-C by 43.6% [mean (standard deviation, SD), 3.4 (3.2) mmol/L] in the overall population; mean LDL-C reduction in adults and adolescents was 41.7% [mean (SD), 3.2 (3.3) mmol/L] and 55.4% [mean (SD), 4.7 (2.5) mmol/L], respectively.

Conclusions: In this large cohort of patients with HoFH, evinacumab was generally well tolerated and markedly decreased LDL-C irrespective of age and sex. Moreover, the efficacy and safety of evinacumab was sustained over the long term.

Keywords: Atherosclerosis; Cholesterol; Homozygous familial hypercholesterolaemia.

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Figures

Structured Graphical Abstract
Structured Graphical Abstract
HoFH, homozygous familial hypercholesterolaemia; IV, intravenous; LDL-C, LDL cholesterol; LDLR, LDL receptor; Lp(a), lipoprotein(a); PCSK9i, proprotein convertase subtilisin/kexin type 9 inhibitor; Q4W, every 4 weeks; SE, standard error; TEAE, treatment-emergent adverse event.
Figure 1
Figure 1
Per cent change in LDL cholesterol from baseline to Week 144 by (A) treatment status and (B) age. LDL-C, LDL cholesterol; SE, standard error
Figure 2
Figure 2
Mean per cent change in LDL cholesterol from baseline to Week 24 by patient subgroup. aNon-Caucasian group comprised patients who self-reported as African American or Black, Asian, and other (including those who did not self-report as African American or Black, Asian, American Indian, or Alaska Native, Native Hawaiian or other Pacific Islander). The non-Caucasian group also included patients for whom race was not reported. bNull–null genotype is defined as <15% LDLR activity. LDL-C, LDL cholesterol; LDLR, LDL receptor; Lp(a), lipoprotein(a); PCSK9, proprotein convertase subtilisin/kexin type 9; SD, standard deviation
Figure 3
Figure 3
Mean per cent change in lipid and lipoprotein parameters from baseline to Week 24. Apo B, apolipoprotein B; HDL-C, HDL cholesterol; LDL-C, LDL cholesterol; Lp(a), lipoprotein(a); SD, standard deviation
See this image and copyright information in PMC

References

    1. Mach F, Baigent C, Catapano AL, Koskinas KC, Casula M, Badimon L, et al. 2019 ESC/EAS guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk. Eur Heart J 2020;41:111–88. 10.1093/eurheartj/ehz455 - DOI - PubMed
    1. Moorjani S, Roy M, Torres A, Betard C, Gagne C, Lambert M, et al. Mutations of low-density-lipoprotein-receptor gene, variation in plasma cholesterol, and expression of coronary heart disease in homozygous familial hypercholesterolaemia. Lancet 1993;341:1303–6. 10.1016/0140-6736(93)90815-X - DOI - PubMed
    1. Nordestgaard BG, Chapman MJ, Humphries SE, Ginsberg HN, Masana L, Descamps OS, et al. Familial hypercholesterolaemia is underdiagnosed and undertreated in the general population: guidance for clinicians to prevent coronary heart disease: consensus statement of the European Atherosclerosis Society. Eur Heart J 2013;34:3478–90. 10.1093/eurheartj/eht273 - DOI - PMC - PubMed
    1. Cuchel M, Bruckert E, Ginsberg HN, Raal FJ, Santos RD, Hegele RA, et al. Homozygous familial hypercholesterolaemia: new insights and guidance for clinicians to improve detection and clinical management. A position paper from the Consensus Panel on Familial Hypercholesterolaemia of the European Atherosclerosis Society. Eur Heart J 2014;35:2146–57. 10.1093/eurheartj/ehu274 - DOI - PMC - PubMed
    1. Bélanger AM, Akioyamen L, Alothman L, Genest J. Evidence for improved survival with treatment of homozygous familial hypercholesterolemia. Curr Opin Lipidol 2020;31:176–81. 10.1097/MOL.0000000000000686 - DOI - PubMed

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