{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T20:49:41Z","timestamp":1791924581612,"version":"4.3.4"},"reference-count":300,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2025,3,20]],"date-time":"2025-03-20T00:00:00Z","timestamp":1742428800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Research, Development and Innovation Office of Hungary","award":["K 132870"],"award-info":[{"award-number":["K 132870"]}]},{"name":"National Research, Development and Innovation Office of Hungary","award":["DETKA"],"award-info":[{"award-number":["DETKA"]}]},{"name":"University of Debrecen Scientific Research Bridging Fund","award":["K 132870"],"award-info":[{"award-number":["K 132870"]}]},{"name":"University of Debrecen Scientific Research Bridging Fund","award":["DETKA"],"award-info":[{"award-number":["DETKA"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>In addition to classic small-molecule drugs and modern protein-based biologics, an intriguing class of medicines is the therapeutic oligonucleotides. Most approved drugs in this category are antisense oligomers or those acting via RNA interference, both of which use base hybridization. Aptamers, also known as chemical antibodies form a smaller, yet equally interesting group of oligonucleotides that can recognize a wide range of molecular targets. Despite their high potential, only two aptamers have been approved to date, pegaptanib (MacugenTM) and avacincaptad pegol (IzervayTM), both for the treatment of age-related macular degeneration (AMD). Targeting vascular endothelial growth factor (VEGF), which plays an important role in the pathogenesis of many eye diseases, pegaptanib emerged as the first anti-VEGF agent and was used in various indications, further inspiring the development of other anti-VEGF therapies. In this review, we summarize the history of the first approved aptamer medicine, pegaptanib. We describe its chemistry and track its development from the earliest stages to the preclinical phase, clinical trials, and eventual regulatory approval. Additionally, we evaluate its position among other therapeutic agents and provide a comprehensive overview of pegaptanib\u2019s efficacy, safety, and cost-effectiveness, comparing these aspects with those of monoclonal antibodies with similar indications, bevacizumab and ranibizumab.<\/jats:p>","DOI":"10.3390\/pharmaceutics17030394","type":"journal-article","created":{"date-parts":[[2025,3,20]],"date-time":"2025-03-20T09:17:39Z","timestamp":1742462259000},"page":"394","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":37,"title":["The 20th Anniversary of Pegaptanib (MacugenTM), the First Approved Aptamer Medicine: History, Recent Advances and Future Prospects of Aptamers in Therapy"],"prefix":"10.3390","volume":"17","author":[{"given":"Mikl\u00f3s","family":"Bege","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Chemistry, University of Debrecen, Egyetem t\u00e9r 1, 4032 Debrecen, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-4896-4880","authenticated-orcid":false,"given":"Rasha","family":"Ghanem Kattoub","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, University of Debrecen, Egyetem t\u00e9r 1, 4032 Debrecen, Hungary"},{"name":"Doctoral School of Pharmaceutical Sciences, Faculty of Pharmacy, University of Debrecen, Nagyerdei krt. 98., 4032 Debrecen, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8462-4547","authenticated-orcid":false,"given":"Anik\u00f3","family":"Borb\u00e1s","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, University of Debrecen, Egyetem t\u00e9r 1, 4032 Debrecen, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,3,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2957","DOI":"10.1158\/1535-7163.MCT-06-0172","article-title":"Discovery and development of anticancer aptamers","volume":"5","author":"Ireson","year":"2006","journal-title":"Mol. 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