{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T07:45:37Z","timestamp":1791359137820,"version":"4.3.1"},"reference-count":16,"publisher":"American Medical Association (AMA)","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Cardiol"],"published-print":{"date-parts":[[2026,2,1]]},"abstract":"<jats:sec>\n                    <jats:title>Importance<\/jats:title>\n                    <jats:p>Homozygous familial hypercholesterolemia (HoFH) is a rare, life-threatening genetic disorder. Patients with HoFH have markedly elevated low-density lipoprotein cholesterol (LDL-C) levels from birth, and their activity of LDL receptor (LDLR) is typically absent or severely impaired. However, efficacy of traditional lipid-regulating agents relies on residual LDLR function. Angiopoietinlike 3 (ANGPTL3)\u2013directed therapies could reduce lipid levels through an LDLR-independent pathway.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To evaluate SHR-1918, a fully human monoclonal antibody targeting ANGPTL3, in adults with HoFH taking stable lipid-lowering therapy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design, Setting, and Participants<\/jats:title>\n                    <jats:p>This was a multicenter, single-arm, phase 2 nonrandomized clinical trial conducted at 8 sites in China between December 19, 2023, and April 2, 2024. Included were participants with HoFH taking stable lipid-lowering therapy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Interventions<\/jats:title>\n                    <jats:p>Patients were given subcutaneous SHR-1918 at 600 mg every 4 weeks for 12 weeks, followed by an 8-week follow-up.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Main Outcomes and Measures<\/jats:title>\n                    <jats:p>The primary end point was the percent change in serum LDL-C level from baseline to week 12.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>A total of 26 patients (mean [SD] age, 36.1 [12.2] years; 16 female [61.5%]) were included in this analysis. The mean (SD) baseline LDL-C level was 433.59 (173.74) mg\/dL. At week 12, the mean percent change in LDL-C level was \u221259.09% (SD, 11.71%; 95% CI, \u221263.81% to \u221254.36%). The reduction was observed throughout the entire 8-week follow-up period. SHR-1918 suggested similar LDL-C reduction across HoFH genotypes, with a percent change from baseline to week 12 of \u221261.32% for homozygous, \u221256.40% for compound heterozygous, and \u221272.21% for double heterozygous. Overall, 16 patients (61.5%) had at least 1 treatment-emergent adverse event, with the most common being proteinuria (4 [15.4%]). Injection site reaction occurred in only 1 patient (3.8%) and included pain and rash or erythema (both grade 1).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions and Relevance<\/jats:title>\n                    <jats:p>Results show that SHR-1918 was associated with a substantial reduction in LDL-C level and favorable safety profile among patients with HoFH taking stable lipid-lowering therapy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial Registration<\/jats:title>\n                    <jats:p>\n                      ClinicalTrials.gov Identifier:\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/www.clinicaltrials.gov\/study\/NCT06009393\">NCT06009393<\/jats:ext-link>\n                    <\/jats:p>\n                  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