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This post-hoc analysis assessed the efficacy of evinacumab in reducing TRLs in patient cohorts from three separate clinical trials with evinacumab.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>Patients with homozygous familial hypercholesterolemia (HoFH) and low-density lipoprotein cholesterol (LDL-C)\u2009\u2265\u200970\u00a0mg\/dL were enrolled in a phase III trial (R1500-CL-1629; NCT03399786). Patients diagnosed with refractory hypercholesterolemia, with LDL-C\u2009\u2265\u200970\u00a0mg\/dL or\u2009\u2265\u2009100\u00a0mg\/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\u2009\u2265\u2009500\u00a0mg\/dL) were enrolled in a phase II trial (R1500-HTG-1522; NCT03452228). Patients received evinacumab intravenously (5 or 15\u00a0mg\/kg) every 4\u00a0weeks, or subcutaneously (300 or 450\u00a0mg) every week or every 2\u00a0weeks. 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\u00a0weeks for trial 1522, 1643, and 1629, respectively.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>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\u2009&gt;\u200950% 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.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>Despite limitations in direct comparisons between study groups, these data indicate that TRL levels could be a future target for lipid-lowering therapies.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1007\/s10557-024-07567-z","type":"journal-article","created":{"date-parts":[[2024,3,6]],"date-time":"2024-03-06T04:02:28Z","timestamp":1709697748000},"page":"925-931","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Evinacumab Reduces Triglyceride-Rich Lipoproteins in Patients with Hyperlipidemia: A Post-Hoc Analysis of Three Randomized Clinical Trials"],"prefix":"10.1007","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5599-0633","authenticated-orcid":false,"given":"Robert S.","family":"Rosenson","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel J.","family":"Rader","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shazia","family":"Ali","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Poulabi","family":"Banerjee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"McGinniss","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Pordy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,3,6]]},"reference":[{"issue":"32","key":"7567_CR1","doi-asserted-by":"publisher","first-page":"2459","DOI":"10.1093\/eurheartj\/ehx144","volume":"38","author":"BA Ference","year":"2017","unstructured":"Ference BA, Ginsberg HN, Graham I, et al. 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For each clinical trial, the study protocol including all amendments were reviewed and approved by the appropriate institutional review board or independent ethics committee at each participating study site. All trials were conducted in accordance with the principles of the Declaration of Helsinki and the International Conference on Harmonization Good Clinical Practice guidelines.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics Approval"}},{"value":"All patients provided written informed consent prior to enrolment in the clinical trials that are reported in this manuscript.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to Participate"}},{"value":"This manuscript does not contain any patient identifiable data, therefore consent for publication is not required.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to Publish"}},{"value":"Robert S. Rosenson reports grants and\/or personal fees outside the submitted work from Regeneron Pharmaceuticals, Inc., Amgen, Arrowhead, Avilar Therapeutics, CRISPR Therapeutics, Kowa, Lilly, Lipigon, Merck, Novartis, Precision BioSciences, UpToDate, UltraGenyx, and Verve Therapeutics; and reports stock holdings in MediMergent, LLC.Daniel J. Rader reports consultancy fees\/honoraria for scientific advisory board participation for Alnylam, Novartis, Pfizer, Regeneron Pharmaceuticals, Inc., and Verve Therapeutics; and has ownership interest\/partnership\/principal in Staten Bio and Vascular Strategies.Shazia Ali, Poulabi Banerjee, Jennifer McGinniss, and Robert Pordy are employees of and shareholders in Regeneron Pharmaceuticals, Inc.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflicts of Interest"}}]}}