{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T08:42:13Z","timestamp":1792226533603,"version":"4.4.0"},"reference-count":45,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"6","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[2019,8,6]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Hypertriglyceridemia is associated with increased cardiovascular risk and may be caused by impaired lipoprotein clearance. Angiopoietin-like protein 3 (ANGPTL3) inhibits lipoprotein lipase activity, increasing triglycerides and other lipids. Evinacumab, an ANGPTL3 inhibitor, reduced triglycerides in healthy human volunteers and in homozygous familial hypercholesterolemic individuals. Results from 2 Phase 1 studies in hypertriglyceridemic subjects are reported here.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>Subjects with triglycerides &gt;150 but \u2264450 mg\/dL and low-density lipoprotein cholesterol \u2265100 mg\/dL (n=83 for single ascending dose study [SAD]; n=56 for multiple ascending dose study [MAD]) were randomized 3:1 to evinacumab:placebo. SAD subjects received evinacumab subcutaneously at 75\/150\/250 mg, or intravenously at 5\/10\/20 mg\/kg, monitored up to day 126. MAD subjects received evinacumab subcutaneously at 150\/300\/450 mg once weekly, 300\/450 mg every 2 weeks, or intravenously at 20 mg\/kg once every 4 weeks up to day 56 with 6 months of follow-up. The primary outcomes were incidence and severity of treatment-emergent adverse events. Efficacy analyses included changes in triglycerides and other lipids over time.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      In the SAD, 32 (51.6%) versus 9 (42.9%) subjects on evinacumab versus placebo reported treatment-emergent adverse events. In the MAD, 21 (67.7%) versus 9 (75.0%) subjects on subcutaneously evinacumab versus placebo and 6 (85.7%) versus 1 (50.0%) on intravenously evinacumab versus placebo reported treatment-emergent adverse events. No serious treatment-emergent adverse events or events leading to death or treatment discontinuation were reported. Elevations in alanine aminotransferase (7 [11.3%] SAD), aspartate aminotransferase (4 [6.5%] SAD), and creatinine phosphokinase (2 [3.2%) SAD, 1 [14.3%] MAD) were observed with evinacumab (none in the placebo groups), which were single elevations and were not dose-related. Dose-dependent reductions in triglycerides were observed in both studies, with maximum reduction of 76.9% at day 3 with 10 mg\/kg intravenously (\n                      <jats:italic>P<\/jats:italic>\n                      &lt;0.0001) in the SAD and of 83.1% at day 2 with 20 mg\/kg intravenously once every 4 weeks (\n                      <jats:italic>P<\/jats:italic>\n                      =0.0003) in the MAD. Significant reductions in other lipids were observed with most evinacumab doses versus placebo.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>\n                      Evinacumab was well-tolerated in 2 Phase 1 studies. Lipid changes in hypertriglyceridemic subjects were similar to those observed with\n                      <jats:italic>ANGPTL3<\/jats:italic>\n                      loss-of-function mutations. Because the latter is associated with reduced cardiovascular risk, ANGPTL3 inhibition may improve clinical outcomes.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Clinical Trial Registration:<\/jats:title>\n                    <jats:p>\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/www.clinicaltrials.gov\">https:\/\/www.clinicaltrials.gov<\/jats:ext-link>\n                      . Unique identifiers: NCT01749878 and NCT02107872.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/circulationaha.118.039107","type":"journal-article","created":{"date-parts":[[2019,6,27]],"date-time":"2019-06-27T05:00:22Z","timestamp":1561611622000},"page":"470-486","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":228,"title":["Inhibition of Angiopoietin-Like Protein 3 With a Monoclonal Antibody Reduces Triglycerides in Hypertriglyceridemia"],"prefix":"10.1161","volume":"140","author":[{"given":"Zahid","family":"Ahmad","sequence":"first","affiliation":[{"name":"Division of Nutrition and Metabolic Diseases, Department of Internal Medicine, Center for Human Nutrition, University of Texas Southwestern Medical Center, Dallas (Z.A.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Poulabi","family":"Banerjee","sequence":"additional","affiliation":[{"name":"Regeneron Pharmaceuticals Inc, Tarrytown, NY (P.B., S.H., K.-C.C., A.B., W.JS., R.P., S.M., H.D., D.A.G.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Hamon","sequence":"additional","affiliation":[{"name":"Regeneron Pharmaceuticals Inc, Tarrytown, NY (P.B., S.H., K.-C.C., A.B., W.JS., R.P., S.M., H.D., D.A.G.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kuo-Chen","family":"Chan","sequence":"additional","affiliation":[{"name":"Regeneron Pharmaceuticals Inc, Tarrytown, NY (P.B., S.H., K.-C.C., A.B., W.JS., R.P., S.M., H.D., D.A.G.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aurelie","family":"Bouzelmat","sequence":"additional","affiliation":[{"name":"Regeneron Pharmaceuticals Inc, Tarrytown, NY (P.B., S.H., K.-C.C., A.B., W.JS., R.P., S.M., H.D., D.A.G.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William J.","family":"Sasiela","sequence":"additional","affiliation":[{"name":"Regeneron Pharmaceuticals Inc, Tarrytown, NY (P.B., S.H., K.-C.C., A.B., W.JS., R.P., S.M., H.D., D.A.G.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Pordy","sequence":"additional","affiliation":[{"name":"Regeneron Pharmaceuticals Inc, Tarrytown, NY (P.B., S.H., K.-C.C., A.B., W.JS., R.P., S.M., H.D., D.A.G.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott","family":"Mellis","sequence":"additional","affiliation":[{"name":"Regeneron Pharmaceuticals Inc, Tarrytown, NY (P.B., S.H., K.-C.C., A.B., W.JS., R.P., S.M., H.D., D.A.G.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hayes","family":"Dansky","sequence":"additional","affiliation":[{"name":"Regeneron Pharmaceuticals Inc, Tarrytown, NY (P.B., S.H., K.-C.C., A.B., W.JS., R.P., S.M., H.D., D.A.G.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel A.","family":"Gipe","sequence":"additional","affiliation":[{"name":"Regeneron Pharmaceuticals Inc, Tarrytown, NY (P.B., S.H., K.-C.C., A.B., W.JS., R.P., S.M., H.D., D.A.G.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard L.","family":"Dunbar","sequence":"additional","affiliation":[{"name":"Division of Translational Medicine and Human Genetics, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia (R.L.D.)."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1177\/174182679600300214"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/s0140-6736(10)60545-4"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1307095"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacl.2015.02.003"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1161\/circ.106.25.3143"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1097\/MPA.0b013e31816074a1"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.4158\/EP171764.GL"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehw272"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1186\/1476-511X-10-157"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbalip.2011.11.010"},{"key":"e_1_3_4_12_2","volume-title":"In: Endotext","author":"Feingold KR","year":"2000","unstructured":"Feingold, KR, Grunfeld, C. 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