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Evinacumab significantly reduces LDL-C in homozygous FH patients

Presented by
Dr F. Raal, University of the Witwatersrand, South Africa
ACC 2020
Results from a phase 3 trial demonstrated that evinacumab substantially lowered low-density lipoprotein cholesterol (LDL-C) in patients with homozygous familial hypercholesterolemia (FH), regardless of LDL receptor function. The PCSK9 inhibitor evinacumab may provide an effective treatment option for patients with homozygous FH who are unable to reach target LDL-C despite multiple conventional lipid lowering therapies with or without apheresis.

Dr Frederick Raal (University of the Witwatersrand, South Africa), who presented the results of this study, explained that evinacumab is a fully human monoclonal antibody inhibitor of ANGPTL3 and reduces LDL-C regardless of the LDL receptor [1]. Patients were eligible if they were 12 years or older and on a stable maximally tolerated lipid-lowering therapy with LDL-C ‚Č•70 mg/dL. Participants were randomised to evinacumab 15 mg/kg IV every 4 weeks (n=43) or placebo (n=22). The primary endpoint of the study was LDL reduction from baseline at 24 weeks.

At 24 weeks, the mean LDL reduction was 47.1% with evinacumab compared with an increase of 1.9% with placebo. This translates into an average relative reduction of 49% in patients receiving evinacumab, meeting the trial’s primary endpoint (P<0.001). For patients who received evinacumab, LDL reductions were similar for those with null/null alleles (n=15) and non-null/null mutations (n=28). At 24 weeks, the absolute change in LDL was 134.7 mg/dL for patients receiving evinacumab versus 2.6 mg/dL for those on placebo (difference of 132.1 mg/dL; P<0.0001).

Adverse events occurred in 65.9% of evinacumab patients versus 81% of placebo patients. Serious adverse events occurred in 4.5% of evinacumab patients while no placebo patients experienced serious adverse events. According to the researchers, events occurring in the evinacumab group were unrelated to the study drug. Several study limitations were pointed out, including the duration, particularly for conclusions regarding the long-term safety of evinacumab, which would presumably be taken life-long. The safety of evinacumab is being further assessed in the open-label treatment period of the trial.

    1. Raal FJ, et al. Abstract 411-12.ACC/WCC 28-30 March 2020.


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