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Evinacumab Reduces Triglyceride-Rich Lipoproteins in Patients with Hyperlipidemia: A Post-Hoc Analysis of Three
Robert S Rosenson1, Daniel J Rader2, Shazia Ali3
1Metabolism and Lipids Unit, Mount Sinai Heart, Icahn School of Medicine at Mount Sinai, 1 Gustave L. Levy Pl, New York, NY, 10029, USA. robert.rosenson@mssm.edu.
Insights
Evinacumab effectively reduced triglyceride-rich lipoproteins (TRLs) in patients with severe hypertriglyceridemia, homozygous familial hypercholesterolemia, and refractory hypercholesterolemia. These findings suggest TRLs are a viable target for future lipid-lowering therapies.
Area of Science:
- Cardiovascular Medicine
- Pharmacology
- Genetics
Background:
- Elevated triglyceride-rich lipoproteins (TRLs) are causally linked to atherosclerotic cardiovascular disease (ASCVD).
- Current lipid-lowering therapies may not sufficiently address TRL-associated ASCVD risk.
Purpose of the Study:
- To assess the efficacy of evinacumab in reducing TRLs across diverse patient cohorts.
- To evaluate evinacumab's impact on lipid parameters in patients with homozygous familial hypercholesterolemia (HoFH), refractory hypercholesterolemia, and severe hypertriglyceridemia.
Main Methods:
- A post-hoc analysis of three clinical trials (NCT03399786, NCT03175367, NCT03452228) involving evinacumab.
- Patients received evinacumab intravenously or subcutaneously at various doses and frequencies.
- Efficacy was measured by changes in TRLs and other lipid parameters from baseline.
Main Results:
- Evinacumab demonstrated significant reductions in TRLs across all studied patient groups.
- Over 50% reduction in TRLs from baseline was observed at higher evinacumab doses in HoFH and refractory hypercholesterolemia cohorts.
- Evinacumab was generally well-tolerated in all trials.
Conclusions:
- TRLs represent a promising therapeutic target for novel lipid-lowering strategies.
- Evinacumab shows potential in managing dyslipidemias associated with increased ASCVD risk.
Purpose:
Natural selection (Mendelian randomization) studies support a causal relationship between elevated triglyceride-rich lipoproteins (TRLs) and atherosclerotic cardiovascular disease (ASCVD). This post-hoc analysis assessed the efficacy of evinacumab in reducing TRLs in patient cohorts from three separate clinical trials with evinacumab.
Methods:
Patients with homozygous familial hypercholesterolemia (HoFH) and low-density lipoprotein cholesterol (LDL-C) ≥ 70 mg/dL were enrolled in a phase III trial (R1500-CL-1629; NCT03399786). Patients diagnosed with refractory hypercholesterolemia, with LDL-C ≥ 70 mg/dL or ≥ 100 mg/dL for those with or without ASCVD, respectively, were enrolled in a phase II trial (R1500-CL-1643; NCT03175367). Patients with severe hypertriglyceridemia (fasting TGs ≥ 500 mg/dL) were enrolled in a phase II trial (R1500-HTG-1522; NCT03452228). Patients received evinacumab intravenously (5 or 15 mg/kg) every 4 weeks, or subcutaneously (300 or 450 mg) every week or every 2 weeks. Efficacy outcomes included change in TRLs (calculated as total cholesterol minus high-density lipoprotein cholesterol minus LDL-C) and other lipid parameters from baseline to 12, 16, or 24 weeks for trial 1522, 1643, and 1629, respectively.
Results:
At baseline, TRL levels were higher for patients with severe hypertriglyceridemia entering the 1522 trial vs. other cohorts. Reductions in TRLs were observed across all studies with evinacumab, with > 50% reduction from baseline observed at the highest doses evaluated in patients with HoFH or refractory hypercholesterolemia. Within all three trials, evinacumab was generally well tolerated.
Conclusions:
Despite limitations in direct comparisons between study groups, these data indicate that TRL levels could be a future target for lipid-lowering therapies.
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