{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T20:59:07Z","timestamp":1793393947093,"version":"4.5.0"},"reference-count":90,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2022,1,1]],"date-time":"2022-01-01T00:00:00Z","timestamp":1640995200000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Apellis Pharmaceuticals, Inc","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Therapeutic Advances in Hematology"],"published-print":{"date-parts":[[2022,1]]},"abstract":"<jats:p>\n                    Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, acquired, hematologic disease characterized by complement-mediated hemolysis, thrombosis, and various degrees of bone marrow dysfunction. Until recently, C5 inhibition with eculizumab or ravulizumab represented the only therapies approved for patients with PNH by the United States Food and Drug Administration (US FDA). Although C5-inhibitors reduce PNH-related signs and symptoms, many patients continue to exhibit persistent anemia and require frequent blood transfusions. In May 2021, pegcetacoplan became the third US FDA-approved treatment for adults with PNH, and the first to target C3, a complement component upstream of C5. The novel strategy of inhibiting proximal complement activity with pegcetacoplan controls C5-mediated intravascular hemolysis and prevents C3-mediated extravascular hemolysis. Here, we review the results from multiple pegcetacoplan clinical studies on the efficacy and safety of pegcetacoplan treatment in adults with PNH. This review summarizes findings from three studies in complement-inhibitor-na\u00efve patients with PNH (PADDOCK [phase Ib], PALOMINO [phase IIa], PRINCE [phase III; pegcetacoplan versus standard treatment excluding complement-inhibitors]), and one phase III study (PEGASUS) that compared eculizumab to pegcetacoplan in patients who remained anemic (hemoglobin levels\u2009&lt;\u200910.5\u2009g\/dL) despite stable eculizumab treatment (\u2a7e3\u2009months). These studies found that pegcetacoplan contributed to superior improvements in primary and secondary endpoints related to hemoglobin levels and other hematologic parameters and provided effective management of anemia and anemia-related complications (i.e. transfusion burden, reticulocyte production, and fatigue). Furthermore, we summarize results from the 32-week open-label period from the PEGASUS trial, which confirmed the long-term safety and durable efficacy of pegcetacoplan as demonstrated by sustained improvements in clinical and hematologic outcomes in pegcetacoplan-treated patients. Pegcetacoplan is approved for the treatment of adults with PNH in the United States (Empaveli\u2122) and for adult patients who remain anemic after at least 3\u2009months of stable C5-inhibitor therapy in the European Union (Aspaveli\n                    <jats:sup>\u00ae<\/jats:sup>\n                    ) and Australia (Empaveli; also approved for patients intolerant to C5-inhibitors).\n                  <\/jats:p>","DOI":"10.1177\/20406207221114673","type":"journal-article","created":{"date-parts":[[2022,7,28]],"date-time":"2022-07-28T06:58:51Z","timestamp":1658991531000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":38,"title":["Safety and efficacy of pegcetacoplan in paroxysmal nocturnal hemoglobinuria"],"prefix":"10.1177","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9011-4268","authenticated-orcid":false,"given":"Raymond S.M.","family":"Wong","sequence":"first","affiliation":[{"name":"Sir Y.K. Pao Centre for Cancer and Department of Medicine & Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, 30-32 Ngan Shing Street, Shatin, Hong Kong"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2022,7,28]]},"reference":[{"key":"bibr1-20406207221114673","doi-asserted-by":"publisher","DOI":"10.1038\/nrdp.2017.28"},{"key":"bibr2-20406207221114673","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2019-125867"},{"key":"bibr3-20406207221114673","volume-title":"Paroxysmal nocturnal hemoglobinuria","author":"Shah N","year":"2021"},{"key":"bibr4-20406207221114673","doi-asserted-by":"publisher","DOI":"10.1111\/ejh.13059"},{"key":"bibr5-20406207221114673","doi-asserted-by":"publisher","DOI":"10.1007\/s00277-020-04052-z"},{"key":"bibr6-20406207221114673","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa061648"},{"key":"bibr7-20406207221114673","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2007-06-094136"},{"key":"bibr8-20406207221114673","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2018-09-876805"},{"key":"bibr9-20406207221114673","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2018-09-876136"},{"key":"bibr10-20406207221114673","doi-asserted-by":"publisher","DOI":"10.1007\/s00277-021-04715-5"},{"key":"bibr11-20406207221114673","doi-asserted-by":"publisher","DOI":"10.1007\/s12185-013-1404-y"},{"key":"bibr12-20406207221114673","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2021-144554"},{"key":"bibr13-20406207221114673","unstructured":"Apellis Pharmaceuticals. EMPAVELI\u2122 (pegcetacoplan) injection, for subcutaneous use. U.S. Prescribing Information, 2021, https:\/\/pi.apellis.com\/files\/PI_Empaveli.pdf"},{"key":"bibr14-20406207221114673","unstructured":"Apellis Pharmaceuticals. Apellis and Sobi announce EU approval of Aspaveli\u00ae (pegcetacoplan) for treatment of PNH, 2021, https:\/\/investors.apellis.com\/news-releases\/news-release-details\/apellis-and-sobi-announce-eu-approval-aspavelir-pegcetacoplan"},{"key":"bibr15-20406207221114673","unstructured":"Australian Government Department of Health and Therapeutic Goods Administration. Empaveli; ARTG 346216, 2022, https:\/\/www.tga.gov.au\/apm-summary\/empaveli"},{"key":"bibr16-20406207221114673","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(93)90250-T"},{"key":"bibr17-20406207221114673","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1994.tb06240.x"},{"key":"bibr18-20406207221114673","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.90.11.5272"},{"key":"bibr19-20406207221114673","doi-asserted-by":"publisher","DOI":"10.1111\/ijlh.13228"},{"key":"bibr20-20406207221114673","doi-asserted-by":"publisher","DOI":"10.1016\/S1040-8428(99)00052-9"},{"key":"bibr21-20406207221114673","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.iy.07.040189.000343"},{"key":"bibr22-20406207221114673","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2015-06-640995"},{"key":"bibr23-20406207221114673","doi-asserted-by":"crossref","first-page":"3478","DOI":"10.4049\/jimmunol.144.9.3478","volume":"144","author":"Rollins SA","year":"1990","journal-title":"J 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WY","year":"2020","journal-title":"Blood"},{"key":"bibr44-20406207221114673","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2019.236877"},{"key":"bibr45-20406207221114673","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0195909"},{"key":"bibr46-20406207221114673","first-page":"3471","volume":"130","author":"McKinley 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Immunol"},{"key":"bibr62-20406207221114673","doi-asserted-by":"publisher","DOI":"10.1021\/jm0603419"},{"key":"bibr63-20406207221114673","doi-asserted-by":"publisher","DOI":"10.1007\/s40265-021-01560-8"},{"key":"bibr64-20406207221114673","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.25960"},{"key":"bibr65-20406207221114673","first-page":"1","volume":"30","author":"Simon-Tillaux N","year":"2019","journal-title":"J Am Soc Nephrol"},{"key":"bibr66-20406207221114673","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2029073"},{"key":"bibr67-20406207221114673","unstructured":"Apellis Pharmaceuticals. A phase I study to assess the safety of pegcetacoplan (APL-2) as an add-on to standard of care in subjects with PNH. Bethesda, MD: National Library of Medicine (U.S.), 2014, https:\/\/clinicaltrials.gov\/ct2\/show\/NCT02264639"},{"key":"bibr68-20406207221114673","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2020-134436"},{"key":"bibr69-20406207221114673","unstructured":"Apellis Pharmaceuticals. A phase IIa study to assess the safety, efficacy, and pharmacokinetics of subcutaneously administered pegcetacoplan (APL-2) in subjects with PNH. Bethesda, MD: National Library of Medicine (U.S.), 2018, https:\/\/clinicaltrials.gov\/ct2\/show\/NCT03593200"},{"key":"bibr70-20406207221114673","unstructured":"Apellis Pharmaceuticals. Pilot study to assess safety, preliminary efficacy and pharmacokinetics of S.C. pegcetacoplan (APL-2) in PNH Subjects. (PADDOCK). Bethesda, MD: National Library of Medicine (U.S.), 2015, https:\/\/clinicaltrials.gov\/ct2\/show\/NCT02588833"},{"key":"bibr71-20406207221114673","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2020-142174"},{"key":"bibr72-20406207221114673","volume":"324582","author":"Peffault de Latour R","year":"2021","journal-title":"EHA Library"},{"key":"bibr73-20406207221114673","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2021-147493"},{"key":"bibr74-20406207221114673","doi-asserted-by":"publisher","DOI":"10.1016\/S2152-2650(21)01793-6"},{"key":"bibr75-20406207221114673","unstructured":"Apellis Pharmaceuticals I. Study to evaluate the efficacy and safety of APL-2 in patients with paroxysmal nocturnal hemoglobinuria (PNH). Bethesda, MD: National Library of Medicine (U.S.), 2018, https:\/\/clinicaltrials.gov\/ct2\/show\/NCT03500549"},{"key":"bibr76-20406207221114673","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2020-134581"},{"key":"bibr77-20406207221114673","volume":"324156","author":"Risitano A","year":"2021","journal-title":"EHA Library"},{"key":"bibr78-20406207221114673","volume":"325355","author":"R\u00f6th A","year":"2021","journal-title":"EHA Library"},{"key":"bibr79-20406207221114673","volume":"324154","author":"Sharma V","year":"2021","journal-title":"EHA Library"},{"key":"bibr80-20406207221114673","unstructured":"Apellis Pharmaceuticals. A study to evaluate the efficacy and safety of pegcetacoplan in patients with PNH. Bethesda, MD: National Library of Medicine (U.S.), 2019, https:\/\/clinicaltrials.gov\/ct2\/show\/NCT04085601"},{"key":"bibr81-20406207221114673","doi-asserted-by":"publisher","DOI":"10.1177\/2040620720966137"},{"key":"bibr82-20406207221114673","unstructured":"Talbird SE, Anderson S, Fishman J, et al. Budget impact of pegcetacoplan, a complement C3 inhibitor, for the treatment of paroxysmal nocturnal hemoglobinuria in us adults. ISPOR EU 2021, https:\/\/www.valueinhealthjournal.com\/article\/S1098-3015(21)02213-0\/fulltext"},{"key":"bibr83-20406207221114673","unstructured":"Apellis Pharmaceuticals. Pegcetacoplan long term safety and efficacy extension study. Bethesda, MD: National Library of Medicine (U.S.), 2018, https:\/\/clinicaltrials.gov\/ct2\/show\/NCT03531255"},{"key":"bibr84-20406207221114673","unstructured":"Apellis Pharmaceuticals. A study of pegcetacoplan in pediatric patients with paroxysmal nocturnal hemoglobinuria (PNH). Bethesda, MD: National Library of Medicine (U.S.), 2021, https:\/\/clinicaltrials.gov\/ct2\/show\/NCT04901936"},{"key":"bibr85-20406207221114673","doi-asserted-by":"publisher","DOI":"10.1016\/j.ophtha.2019.07.011"},{"key":"bibr86-20406207221114673","unstructured":"Apellis Pharmaceuticals. Apellis announces detailed results from Phase 3 DERBY and OAKS studies. Presented at Retina Society Annual Meeting, Apellis Pharmaceuticals Inc Press Release, 2021, https:\/\/investors.apellis.com\/news-releases\/news-release-details\/apellis-announces-detailed-results-phase-3-derby-and-oaks"},{"key":"bibr87-20406207221114673","unstructured":"Apellis Pharmaceuticals. Apellis announces pegcetacoplan showed continuous and clinically meaningful effects at month 18 in phase 3 DERBY and OAKS studies for geographic atrophy (GA). Apellis Pharmaceuticals Inc Press Release, 2022, https:\/\/www.globenewswire.com\/news-release\/2022\/03\/16\/2404200\/0\/en\/Apellis-Announces-Pegcetacoplan-Showed-Continuous-and-Clinically-Meaningful-Effects-at-Month-18-in-Phase-3-DERBY-and-OAKS-Studies-for-Geographic-Atrophy-GA.html"},{"key":"bibr88-20406207221114673","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1681\/ASN.20203110S1577a","volume":"31","author":"Dixon BP","year":"2020","journal-title":"J Am Soc Nephrol"},{"key":"bibr89-20406207221114673","volume":"324156","author":"Gertz M","year":"2019","journal-title":"EHA Library"},{"key":"bibr90-20406207221114673","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.176.3.1305"}],"container-title":["Therapeutic Advances in Hematology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/20406207221114673","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/20406207221114673","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/20406207221114673","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T23:16:16Z","timestamp":1777590976000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/20406207221114673"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,1]]},"references-count":90,"alternative-id":["10.1177\/20406207221114673"],"URL":"https:\/\/doi.org\/10.1177\/20406207221114673","relation":{},"ISSN":["2040-6207","2040-6215"],"issn-type":[{"value":"2040-6207","type":"print"},{"value":"2040-6215","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,1]]},"article-number":"20406207221114673"}}