{"doi":"10.1016/j.jacl.2025.06.004","title":"Pelacarsen: Mechanism of action and Lp(a)-lowering effect","abstract":null,"journal":"Journal of Clinical Lipidology","year":2025,"id":617255,"datarank":0.43441506249115674,"base_score":2.5649493574615367,"endowment":2.5649493574615367,"self_citation_contribution":0.38474240361923057,"citation_network_contribution":0.0496726588719262,"self_endowment_contribution":0.38474240361923057,"citer_contribution":0.0496726588719262,"corpus_percentile":null,"corpus_rank":null,"citation_count":12,"citer_count":12,"citers_with_citation_signal":3,"citers_with_endowment":3,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":493530,"name":"Archna Bajaj","orcid":"0000-0001-7397-6520","position":1,"is_corresponding":false},{"id":404379,"name":"Sascha N. Goonewardena","orcid":"0000-0002-3772-8818","position":2,"is_corresponding":false},{"id":598690,"name":"Patrick M. Moriarty","orcid":"0000-0001-5548-4493","position":3,"is_corresponding":false},{"id":367211,"name":"Harpreet Bhatia","orcid":"0000-0002-3964-2989","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Pelacarsen: Mechanism of action and Lp(a)-lowering effect","abstract":"<h4>Background</h4>Lipoprotein(a) (Lp[a]) is an apolipoprotein B100 (apoB)-containing lipoprotein with a single apolipoprotein(a) (apo[a]) covalently bound to apoB via a disulfide bond and oxidized phospholipids linked to apoB and apo(a), which is associated with proinflammatory, prothrombotic, and proatherogenic mechanisms. Elevated Lp(a) (≥125 nmol/L [≥50 mg/dL]) is an independent, causal, genetically determined risk factor for atherosclerotic cardiovascular disease (ASCVD), affecting >1.4 billion individuals worldwide.<h4>Sources of material</h4>There are no pharmacological Lp(a)-lowering therapies approved in the United States; however, lipoprotein apheresis may be considered under certain circumstances. Germany is the only country where apheresis is approved for patients with elevated Lp(a) and progressing ASCVD.<h4>Abstract of findings</h4>Existing lipid-lowering therapies including proprotein convertase subtilisin/kexin type 9 inhibitors have shown modest effects on Lp(a) levels but fallen short of clinically meaningful reductions of >50 to 100 mg/dL. Several Lp(a)-lowering, RNA-targeted agents are in development, including antisense oligonucleotides (ASOs) and small interfering RNAs. Pelacarsen is a second-generation ASO that targets the production of apo(a) and includes chemical modifications such as triantennary N-acetylgalactosamine that improve biostability, decrease off-target toxicity compared with unmodified ASOs, and allow rapid, specific uptake by hepatocytes, the site of apo(a) synthesis. A phase 2b study of pelacarsen showed ≥80% reduction in Lp(a) concentration with a favorable safety profile in patients with established ASCVD.<h4>Conclusion</h4>The ongoing phase 3 Lp(a)HORIZON study is evaluating whether the Lp(a)-lowering effects of pelacarsen translate into reductions in the incidence of major cardiovascular events, also in patients with established ASCVD. Herein, we review the mechanism of action of pelacarsen and evidence for its Lp(a)-lowering effects.","is_dataset_classified":null,"base_score":2.5649493574615367,"endowment":2.5649493574615367,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"40781022","pmcid":null,"openalex_id":"https://openalex.org/W4411341663","authors":[],"funders":[{"funder_name":"Novartis Pharmaceuticals Corporation","grant_id":"","title":null}],"total_grants":1,"fwci":13.2811,"citation_percentile":0.99218881,"influential_citations":0,"citation_trend":[{"year":2025,"count":4},{"year":2026,"count":8}],"oa_status":"closed","license":"http://creativecommons.org/licenses/by-nc-nd/4.0/","oa_locations":[{"url":"https://api.elsevier.com/content/article/PII:S1933287425003228?httpAccept=text/xml","host_type":"publisher"},{"url":"https://api.elsevier.com/content/article/PII:S1933287425003228?httpAccept=text/plain","host_type":"publisher"},{"url":"https://doi.org/10.1016/j.jacl.2025.06.004","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/40781022","host_type":"repository"}],"fields_of_study":["Lipoproteins and Cardiovascular Health","Diabetes, Cardiovascular Risks, and Lipoproteins","Cholesterol and Lipid Metabolism"],"mesh_terms":["Hypolipidemic Agents","Humans","Oligonucleotides","Oligonucleotides, Antisense","Lipoprotein(a)","Atherosclerosis"],"keywords":["Medicine","Mechanism (biology)","Action (physics)","Mechanism of action","Pharmacology","Genetics","Epistemology","Quantum mechanics","Antisense oligonucleotide","Lipoprotein(a)","Cardiovascular Risk","Atherosclerotic Cardiovascular Disease","Pelacarsen"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-03T01:13:36.764674Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}