{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T04:59:46Z","timestamp":1790139586549,"version":"4.0.1"},"reference-count":20,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,6,26]],"date-time":"2024-06-26T00:00:00Z","timestamp":1719360000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,6,26]],"date-time":"2024-06-26T00:00:00Z","timestamp":1719360000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"SamChunDang Pharm. Co. Ltd"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>To compare the efficacy and safety of the proposed aflibercept biosimilar SCD411 and reference aflibercept in patients with neovascular age-related macular degeneration, this randomized, double-masked, parallel-group, multicenter study was conducted in 14 countries from 13 August 2020 to 8 September 2022. Patients with neovascular age-related macular degeneration. With subfoveal, juxtafoveal, or extrafoveal choroidal neovascularization were aged 50\u00a0years or older. Intravitreal injection of SCD411 or aflibercept (2.0\u00a0mg) were administered every 4\u00a0weeks for the first three injections and every 8\u00a0weeks until week 48. The primary efficacy endpoint was the change in best-corrected visual acuity from baseline to week 8 with an adjusted equivalence margin of\u2009\u00b1\u20093.0 letters. Patients were randomly assigned to receive either SCD411 (n\u2009=\u2009288) or reference aflibercept (n\u2009=\u2009288). A total of 566 participants (98.3%) completed week 8 of the study. The least-squares mean difference of change in best-corrected visual acuity from baseline to week 8 (SCD411\u2014aflibercept) was\u2009\u2212\u20090.4 letters (90% confidence interval\u2009=\u2009\u2009\u2212\u20091.6 to 0.9). The incidence of ocular (69 of 287 [24.0%] vs. 71 of 286 [24.8%]) and serious ocular (5 of 287 [1.7%] vs. 3 of 286 [1.0%]) treatment-emergent adverse effects were similar between the SCD411 and aflibercept groups. Immunogenicity analysis revealed a low incidence of neutralizing antibody formation in both groups. In conclusion, SCD411 has equivalent efficacy compared with reference aflibercept in patients with neovascular age-related macular degeneration and has a comparable safety profile. The results support the potential use of SCD411 for the treatment of neovascular age-related macular degeneration.<\/jats:p>","DOI":"10.1038\/s41598-024-65815-6","type":"journal-article","created":{"date-parts":[[2024,6,26]],"date-time":"2024-06-26T14:02:29Z","timestamp":1719410549000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Comparison of the efficacy and safety of SCD411 and reference aflibercept in patients with neovascular age-related macular degeneration"],"prefix":"10.1038","volume":"14","author":[{"given":"Se Woong","family":"Kang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaehwan","family":"Choi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veeral S.","family":"Sheth","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agnieszka","family":"Nowosielska","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Misiuk-Hojlo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andr\u00e1s","family":"Papp","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David M.","family":"Brown","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jae-Ho","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoreh","family":"Barak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,6,26]]},"reference":[{"key":"65815_CR1","doi-asserted-by":"publisher","first-page":"504","DOI":"10.1016\/j.ajo.2003.11.026","volume":"137","author":"FG Holz","year":"2004","unstructured":"Holz, F. G., Pauleikhoff, D., Klein, R. & Bird, A. C. Pathogenesis of lesions in late age-related macular disease. Am. J. Ophthalmol. 137, 504\u2013510. https:\/\/doi.org\/10.1016\/j.ajo.2003.11.026 (2004).","journal-title":"Am. J. Ophthalmol."},{"key":"65815_CR2","doi-asserted-by":"publisher","first-page":"363","DOI":"10.1016\/j.ophtha.2005.11.019","volume":"113","author":"RL Avery","year":"2006","unstructured":"Avery, R. L. et al. Intravitreal bevacizumab (Avastin) for neovascular age-related macular degeneration. Ophthalmology 113, 363\u2013372. https:\/\/doi.org\/10.1016\/j.ophtha.2005.11.019 (2006).","journal-title":"Ophthalmology"},{"key":"65815_CR3","doi-asserted-by":"publisher","first-page":"1419","DOI":"10.1056\/nejmoa054481","volume":"355","author":"PJ Rosenfeld","year":"2006","unstructured":"Rosenfeld, P. J. et al. Ranibizumab for neovascular age-related macular degeneration. N. Engl. J. Med. 355, 1419\u20131431. https:\/\/doi.org\/10.1056\/nejmoa054481 (2006).","journal-title":"N. Engl. J. Med."},{"key":"65815_CR4","doi-asserted-by":"publisher","first-page":"2537","DOI":"10.1016\/j.ophtha.2012.09.006","volume":"119","author":"JS Heier","year":"2012","unstructured":"Heier, J. S. et al. Intravitreal aflibercept (VEGF trap-eye) in wet age-related macular degeneration. Ophthalmology 119, 2537\u20132548. https:\/\/doi.org\/10.1016\/j.ophtha.2012.09.006 (2012).","journal-title":"Ophthalmology"},{"key":"65815_CR5","unstructured":"Drugs@FDA: FDA-Approved Drugs: Eylea. US Food and Drug Administration. https:\/\/www.accessdata.fda.gov\/scripts\/cder\/daf\/index.cfm?event=overview.process&ApplNo=125387 (Accessed 9 April 2023)."},{"key":"65815_CR6","unstructured":"Eylea. European Medicines Agency. https:\/\/www.ema.europa.eu\/en\/medicines\/human\/EPAR\/eylea#authorisation-details-section (Accessed 9 April 2023)."},{"key":"65815_CR7","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1007\/s10456-011-9249-6","volume":"15","author":"N Papadopoulos","year":"2012","unstructured":"Papadopoulos, N. et al. Binding and neutralization of vascular endothelial growth factor (VEGF) and related ligands by VEGF Trap, ranibizumab and bevacizumab. Angiogenesis 15, 171\u2013185. https:\/\/doi.org\/10.1007\/s10456-011-9249-6 (2012).","journal-title":"Angiogenesis"},{"key":"65815_CR8","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1586\/17512433.2014.884458","volume":"7","author":"MW Stewart","year":"2014","unstructured":"Stewart, M. W. Pharmacokinetics, pharmacodynamics and pre-clinical characteristics of ophthalmic drugs that bind VEGF. Expert Rev. Clin. Pharmacol. 7, 167\u2013180. https:\/\/doi.org\/10.1586\/17512433.2014.884458 (2014).","journal-title":"Expert Rev. Clin. Pharmacol."},{"key":"65815_CR9","doi-asserted-by":"publisher","first-page":"1090","DOI":"10.1016\/s0140-6736(18)32291-8","volume":"392","author":"T Lancet","year":"2018","unstructured":"Lancet, T. Age-related macular degeneration: Treatment at what cost? Lancet 392, 1090. https:\/\/doi.org\/10.1016\/s0140-6736(18)32291-8 (2018).","journal-title":"Lancet"},{"key":"65815_CR10","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1186\/s40942-021-00343-3","volume":"8","author":"M Kapur","year":"2022","unstructured":"Kapur, M., Nirula, S. & Naik, M. P. Future of anti-VEGF: Biosimilars and biobetters. Int. J. Retina Vitreous 8, 3. https:\/\/doi.org\/10.1186\/s40942-021-00343-3 (2022).","journal-title":"Int. J. Retina Vitreous"},{"key":"65815_CR11","doi-asserted-by":"publisher","first-page":"671","DOI":"10.1007\/s40265-017-0717-1","volume":"77","author":"P Declerck","year":"2017","unstructured":"Declerck, P., Danesi, R., Petersel, D. & Jacobs, I. The language of biosimilars: Clarification, definitions, and regulatory aspects. Drugs 77, 671\u2013677. https:\/\/doi.org\/10.1007\/s40265-017-0717-1 (2017).","journal-title":"Drugs"},{"key":"65815_CR12","doi-asserted-by":"publisher","first-page":"1053","DOI":"10.1185\/03007995.2012.686902","volume":"28","author":"JF Lee","year":"2012","unstructured":"Lee, J. F., Litten, J. B. & Grampp, G. Comparability and biosimilarity: Considerations for the healthcare provider. Curr. Med. Res. Opin. 28, 1053\u20131058. https:\/\/doi.org\/10.1185\/03007995.2012.686902 (2012).","journal-title":"Curr. Med. Res. Opin."},{"key":"65815_CR13","doi-asserted-by":"publisher","first-page":"1432","DOI":"10.1056\/nejmoa062655","volume":"355","author":"DM Brown","year":"2006","unstructured":"Brown, D. M. et al. Ranibizumab versus verteporfin for neovascular age-related macular degeneration. N. Engl. J. Med. 355, 1432\u20131444. https:\/\/doi.org\/10.1056\/nejmoa062655 (2006).","journal-title":"N. Engl. J. Med."},{"key":"65815_CR14","doi-asserted-by":"publisher","first-page":"402","DOI":"10.1111\/j.1365-2125.2011.04015.x","volume":"72","author":"H-T Thai","year":"2011","unstructured":"Thai, H.-T. et al. A mechanism-based model for the population pharmacokinetics of free and bound aflibercept in healthy subjects. Br. J. Clin. Pharmacol. 72, 402\u2013414. https:\/\/doi.org\/10.1111\/j.1365-2125.2011.04015.x (2011).","journal-title":"Br. J. Clin. Pharmacol."},{"key":"65815_CR15","doi-asserted-by":"publisher","first-page":"1636","DOI":"10.1136\/bjophthalmol-2014-305252","volume":"98","author":"RL Avery","year":"2014","unstructured":"Avery, R. L. et al. Systemic pharmacokinetics following intravitreal injections of ranibizumab, bevacizumab or aflibercept in patients with neovascular AMD. Br. J. Ophthalmol. 98, 1636\u20131641. https:\/\/doi.org\/10.1136\/bjophthalmol-2014-305252 (2014).","journal-title":"Br. J. Ophthalmol."},{"key":"65815_CR16","doi-asserted-by":"publisher","first-page":"1897","DOI":"10.1056\/NEJMoa1102673","volume":"364","author":"DF Martin","year":"2011","unstructured":"Martin, D. F. et al. Ranibizumab and bevacizumab for neovascular age-related macular degeneration. N. Engl. J. Med. 364, 1897\u20131908. https:\/\/doi.org\/10.1056\/NEJMoa1102673 (2011).","journal-title":"N. Engl. J. Med."},{"key":"65815_CR17","doi-asserted-by":"publisher","first-page":"1911","DOI":"10.1097\/iae.0000000000003128","volume":"41","author":"P Mitchell","year":"2021","unstructured":"Mitchell, P. et al. Efficacy and safety of intravitreal aflibercept using a treat-and-extend regimen for neovascular age-related macular degeneration: The ARIES study: A randomized clinical trial. Retina 41, 1911\u20131920. https:\/\/doi.org\/10.1097\/iae.0000000000003128 (2021).","journal-title":"Retina"},{"key":"65815_CR18","doi-asserted-by":"publisher","first-page":"2292","DOI":"10.1016\/j.ophtha.2013.03.046","volume":"120","author":"S Rofagha","year":"2013","unstructured":"Rofagha, S., Bhisitkul, R. B., Boyer, D. S., Sadda, S. R. & Zhang, K. Seven-year outcomes in ranibizumab-treated patients in ANCHOR, MARINA, and HORIZON: A multicenter cohort study (SEVEN-UP). Ophthalmology 120, 2292\u20132299. https:\/\/doi.org\/10.1016\/j.ophtha.2013.03.046 (2013).","journal-title":"Ophthalmology"},{"key":"65815_CR19","doi-asserted-by":"publisher","first-page":"220","DOI":"10.1136\/bjophthalmol-2014-305327","volume":"99","author":"FG Holz","year":"2015","unstructured":"Holz, F. G. et al. Multi-country real-life experience of anti-vascular endothelial growth factor therapy for wet age-related macular degeneration. Br. J. Ophthalmol. 99, 220\u2013226. https:\/\/doi.org\/10.1136\/bjophthalmol-2014-305327 (2015).","journal-title":"Br. J. Ophthalmol."},{"key":"65815_CR20","doi-asserted-by":"publisher","first-page":"667","DOI":"10.1136\/bjo.2007.134874","volume":"92","author":"MW Stewart","year":"2008","unstructured":"Stewart, M. W. & Rosenfeld, P. J. Predicted biological activity of intravitreal VEGF Trap. Br. J. Ophthalmol. 92, 667\u2013668. https:\/\/doi.org\/10.1136\/bjo.2007.134874 (2008).","journal-title":"Br. J. Ophthalmol."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-024-65815-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-024-65815-6","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-024-65815-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,6,26]],"date-time":"2024-06-26T14:21:58Z","timestamp":1719411718000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-024-65815-6"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,6,26]]},"references-count":20,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["65815"],"URL":"https:\/\/doi.org\/10.1038\/s41598-024-65815-6","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,6,26]]},"assertion":[{"value":"11 July 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"24 June 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"26 June 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"S. W. K. received Grants from Novartis, Bayer, Samsung Bioepis, Roche, Altos Biologics, Opthea, Alexion Pharmaceuticals Inc., Hanlim Pharm. Co. Ltd., and SamChunDang Pharm. Co. Ltd. and serves as a board member and consultant for Bayer, Novartis, Roche, and SamChunDang Pharm. Co. Ltd. J. C. received non-financial supports from SamChunDang Pharm. Co. Ltd. V. S. S. received Grants from SamChunDang Pharm. Co. Ltd., Allergan, Opthea, Oxurion, Recens Medical, Roche, Regenxbio, Eyepoint, Genentech, Ionis, Novartis, Regeneron, Santen, Gyroscope, Chengdu Kanghong, SalutarisMD, NGM Biopharmaceuticals, Alimera Sciences, Outlook, 4D Molecular Therapeutics, Ashvattha Therapeutics, Olix pharmaceuticals, Janssen, and OcuTerra and received consulting fee from Genentech, Novartis, Alimera, EyePoint, Graybug, Apellis, Regeneron, and Vial and received payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Genentech, Alimera, and Apellis. A. N. received travel grant from Bausch & Lomb and serves as a board member of Klinka Oczna and received equipment, materials, drugs, medical writing, gifts or other services from Kodiac, Ora, Altos, Xbrain, and Quilu. M. M. received grant from SamChunDang Pharm. Co. Ltd. A. P. received grants from Bayer, Novartis, Iveric Bio, Samsung Bioepis, Amgen, Oculis, Quilu, Roche, Xbrain, Formycon, Regeneron, Altos Biologics, Shanghai Henlius Biotech Inc., Kodiak Sciences Inc., Intas Pharmaceuticals Ltd., and SamChunDang Pharm. Co. Ltd. and received consulting fees from Bayer, Novartis, Roche, and Formycon and received payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Bayer, Novartis, and Roche and received travel grant from Novartis and serves as a board member of Bayer, Novartis, and Roche and a president of retina section of the Hungarian Ophthalmic Society. D. M. B. received grants from Adverum, Alderya, Alexion, Alkahest, Alimera, Amgen, Annexon, Apellis, Aura, Bayer, Boston Image Reading Center, Boehringer Ingelheim, Clearside Biomedical, Cleveland Clinic Foundation, Eyepoint, Gemini, Genentech\/Roche, Graybug, Gyroscope, John Hopkins, Ionis, Irenix, Iveric, Kodiak, Lowery Medical Research Group, Lumithera, Nanoscope, NEI\/NH, Neurotech, NGM, Novartis, Ocular Therapeutix, Ocuphire Pharma, Inc., OIRRC, ONS, Opthea, Opthotech, OPTOS, Oxurion, Oysterpoint, Regeneron, REGENXBIO, Roche, SamChunDang Pharm. Co. Ltd., Samsung, Sandoz, Santen, Senju, Stealth, Unity, Xbrane, and Zeiss and serves as a consultant for 4DMT, Adverum Biotechnologies Inc., AGTC, Alexion Pharmaceuticals Inc., Annexon Inc., Apellis Pharmaceuticals Inc., Bayer, Biogen MA Inc., Boehringer Ingelheim, Celltrion Inc., Chengdu Kanghong Pharmaceutical, Clearside Biomedical Inc., Coherus BioScience Inc., Gemini Therapeutics Inc., Glaukos, Heidelberg Engineering Inc., Iveric Bio Inc., Kodiak Sciences Inc., Lineage Cell Therapeutics, Medscape LLC, Molecular Partners AG, Novartis Pharma AG, Ocular Therapeutix, Ocuphire Pharma Inc., OPTOS PLC, Pontifax, PPD, Regeneron Pharmaceuticals Inc., RetinAI Medical AG, Ray Therapeutics Inc., SIMR Biotech, Samsung Bioepis Co. Ltd., Senju Pharmaceuticals Co.Ltd., SciNeuro Therapeutics Inc., Smilebiotek Zhuhai Limited, Stealth BioTherapeutics Inc., Verseon, and WebMD Global LLC and holds stock options in Adverum and Clearside Biomedical Inc. J. L. is an employee of SamChunDang Pharm. Co. Ltd. Y. B. received grant from SamChunDang Pharm. Co. Ltd.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"14752"}}