{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"volume":["39(4)"],"submitter":["Rosenson RS"],"funding":["Regeneron Pharmaceuticals"],"pubmed_abstract":["<h4>Purpose</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>Despite limitations in direct comparisons between study groups, these data indicate that TRL levels could be a future target for lipid-lowering therapies."],"journal":["Cardiovascular drugs and therapy"],"pagination":["925-931"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12297002"],"repository":["biostudies-literature"],"pubmed_title":["Evinacumab Reduces Triglyceride-Rich Lipoproteins in Patients with Hyperlipidemia: A Post-Hoc Analysis of Three Randomized Clinical Trials."],"pmcid":["PMC12297002"],"pubmed_authors":["Rader DJ","Ali S","Pordy R","Rosenson RS","McGinniss J","Banerjee P"],"additional_accession":[]},"is_claimable":false,"name":"Evinacumab Reduces Triglyceride-Rich Lipoproteins in Patients with Hyperlipidemia: A Post-Hoc Analysis of Three Randomized Clinical Trials.","description":"<h4>Purpose</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>Despite limitations in direct comparisons between study groups, these data indicate that TRL levels could be a future target for lipid-lowering therapies.","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Aug","modification":"2026-07-05T03:17:44.81Z","creation":"2025-08-13T03:04:21.317Z"},"accession":"S-EPMC12297002","cross_references":{"pubmed":["38446275"],"doi":["10.1007/s10557-024-07567-z"]}}