Evinacumab Reduces Triglyceride-Rich Lipoproteins in Patients with Hyperlipidemia : A Post-Hoc Analysis of Three Randomized Clinical Trials
© 2024. The Author(s)..
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - year:2024 |
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| Enthalten in: |
Cardiovascular drugs and therapy - (2024) vom: 06. März |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Rosenson, Robert S [VerfasserIn] |
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| Links: |
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| Themen: |
Clinical trials |
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| Anmerkungen: |
Date Revised 06.03.2024 published: Print-Electronic Citation Status Publisher |
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| doi: |
10.1007/s10557-024-07567-z |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM369361083 |
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| 100 | 1 | |a Rosenson, Robert S |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Evinacumab Reduces Triglyceride-Rich Lipoproteins in Patients with Hyperlipidemia |b A Post-Hoc Analysis of Three Randomized Clinical Trials |
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| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status Publisher | ||
| 520 | |a © 2024. The Author(s). | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a CONCLUSIONS: Despite limitations in direct comparisons between study groups, these data indicate that TRL levels could be a future target for lipid-lowering therapies | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Clinical trials | |
| 650 | 4 | |a Evinacumab | |
| 650 | 4 | |a Hypercholesterolemia | |
| 650 | 4 | |a Hypertriglyceridemia | |
| 650 | 4 | |a Triglyceride-rich lipoproteins | |
| 700 | 1 | |a Rader, Daniel J |e verfasserin |4 aut | |
| 700 | 1 | |a Ali, Shazia |e verfasserin |4 aut | |
| 700 | 1 | |a Banerjee, Poulabi |e verfasserin |4 aut | |
| 700 | 1 | |a McGinniss, Jennifer |e verfasserin |4 aut | |
| 700 | 1 | |a Pordy, Robert |e verfasserin |4 aut | |
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