{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T00:58:35Z","timestamp":1785200315092,"version":"3.55.0"},"reference-count":22,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2024,11,5]],"date-time":"2024-11-05T00:00:00Z","timestamp":1730764800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100019531","name":"Apellis Pharmaceuticals","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100019531","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["CPT Pharmacom &amp; Syst Pharma"],"published-print":{"date-parts":[[2025,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Pegcetacoplan is a complement C3\/C3b inhibitor indicated for the treatment of geographic atrophy (GA). A population pharmacokinetic (PK)\/pharmacodynamic (PD) analysis of pegcetacoplan used GA lesion area measurements from three clinical studies to determine the effect of pegcetacoplan exposure on GA progression. A base disease progression model was developed using data from sham\u2010treated eyes and untreated fellow eyes, followed by treatment effect assessment in dose\u2013response and PK\/PD models. In total, 1501 patients from FILLY (NCT02503332), OAKS (NCT03525613), and DERBY (NCT03525600) received intravitreal pegcetacoplan 15\u2009mg monthly or every other month (EOM) or sham treatment monthly or EOM and were included in the population analysis of lesion area. Disease progression over time was adequately described as linear\u2010with\u2010time over the 24\u2010month maximal study duration. Disease\u2010specific covariates associated with slower lesion growth were unilateral, unifocal, and subfoveal GA lesions and &gt;20 intermediate or large drusen groups (\u226563\u2009\u03bcm) at baseline. The dose\u2013response model estimated 0.80\u2010fold (95% CI: 0.75, 0.84) and 0.83\u2010fold (95% CI: 0.78, 0.87) reductions in GA lesion growth rate with pegcetacoplan monthly and EOM, respectively, versus sham. A relationship between vitreous humor concentration and GA lesion growth rate was quantified as 2.6% per unit of log\u2010transformed vitreous pegcetacoplan concentration in the PK\/PD model. PK\/PD predictions of treatment effect based on exposure (pegcetacoplan monthly: 0.80 [90% CI: 0.77, 0.84]; pegcetacoplan EOM: 0.83 [90% CI: 0.80, 0.86]) were consistent with predictions based on dose response. These results support the benefit of pegcetacoplan administered monthly or EOM in slowing GA lesion growth.<\/jats:p>","DOI":"10.1002\/psp4.13264","type":"journal-article","created":{"date-parts":[[2024,11,5]],"date-time":"2024-11-05T08:44:28Z","timestamp":1730796268000},"page":"257-267","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Pharmacokinetic\/pharmacodynamic analysis of geographic atrophy lesion area in patients receiving pegcetacoplan treatment or sham"],"prefix":"10.1002","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5403-4730","authenticated-orcid":false,"given":"Ryan L.","family":"Crass","sequence":"first","affiliation":[{"name":"A2\u2010Ai  Ann Arbor Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Komal","family":"Prem","sequence":"additional","affiliation":[{"name":"Apellis Pharmaceuticals  Waltham Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-7184-8008","authenticated-orcid":false,"given":"Francois","family":"Gaudreault","sequence":"additional","affiliation":[{"name":"Apellis Pharmaceuticals  Waltham Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-2519-7511","authenticated-orcid":false,"given":"Elizabeth","family":"Lusk","sequence":"additional","affiliation":[{"name":"A2\u2010Ai  Ann Arbor Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramiro","family":"Ribeiro","sequence":"additional","affiliation":[{"name":"Apellis Pharmaceuticals  Waltham Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sunny","family":"Chapel","sequence":"additional","affiliation":[{"name":"A2\u2010Ai  Ann Arbor Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3651-8210","authenticated-orcid":false,"given":"Caroline R.","family":"Baumal","sequence":"additional","affiliation":[{"name":"Apellis Pharmaceuticals  Waltham Massachusetts USA"},{"name":"New England Eye Center  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,11,5]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ophtha.2017.08.038"},{"issue":"1","key":"e_1_2_11_3_1","first-page":"1","article-title":"Patient\u2010, caregiver\u2010, and eye care professional\u2010reported burden of geographic atrophy secondary to age\u2010related macular degeneration","volume":"2","author":"Singh RP","year":"2019","journal-title":"Am J Ophthmol Clin Trials"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ophtha.2013.11.023"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.2147\/OPTH.S226425"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ophtha.2008.03.009"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ophtha.2019.07.011"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1097\/IAE.0000000000001392"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.18553\/jmcp.2023.29.5-a.s2"},{"key":"e_1_2_11_10_1","unstructured":"Syfovre [package insert].2023. Waltham MA: Apellis Pharmaceuticals Inc."},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.2147\/JBM.S362220"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajo.2021.08.018"},{"key":"e_1_2_11_13_1","unstructured":"CrassRL SmithB EplingD ChapelS PremK GaudreaultF.Population pharmacokinetics of pegcetacoplan in patients with neovascular age\u2010related macular degeneration and geographic atrophy. 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