{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T22:25:35Z","timestamp":1768515935617,"version":"3.49.0"},"reference-count":31,"publisher":"Springer Science and Business Media LLC","issue":"12","license":[{"start":{"date-parts":[[2023,10,10]],"date-time":"2023-10-10T00:00:00Z","timestamp":1696896000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2023,10,10]],"date-time":"2023-10-10T00:00:00Z","timestamp":1696896000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100002429","name":"Amgen","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100002429","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Ann Hematol"],"published-print":{"date-parts":[[2023,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>ABP 959 is being developed as a biosimilar to Soliris\u00ae (eculizumab) reference product (RP), which was approved under orphan designation for a group of rare diseases including paroxysmal nocturnal hemoglobinuria (PNH), atypical hemolytic uremic syndrome (aHUS), generalized myasthenia gravis (gMG), and neuromyelitis optica spectrum disorder (NMOSD). Development of biosimilars for therapeutics approved for rare disease indications must provide scientific rationale based on the totality of evidence (TOE). To support the TOE and the scientific justification for extrapolation to all approved indications for eculizumab RP, including but not limited to aHUS and NMOSD, we utilized simulated ex-vivo pharmacodynamic (PD) assessments to compare the complement component 5 (C5) inhibitory activity of ABP 959 and the RP. Hemolysis activity of CH50 and AH50, and Wieslab CP, AP, and LP endpoints represent the three complement activation pathways (classical, alternative, and\u00a0lectin), all of which share the terminal pathway and require C5 for activity. These endpoints were evaluated in normal serum, simulated aHUS serum, and simulated NMOSD serum to provide a robust comparison. The results support the conclusion that ABP 959 and eculizumab RP exhibit highly similar inhibition of C5 function regardless of the type of\u00a0serum used. This work presents a full comparison of the effect of C5 inhibition across five complement functional assays. Using this approach to confirm functional similarity of ABP 959 with eculizumab RP contributes to the TOE for biosimilarity and provides support for extrapolation based on inhibition of C5 function to other rare disease indications approved for eculizumab RP.<\/jats:p>","DOI":"10.1007\/s00277-023-05439-4","type":"journal-article","created":{"date-parts":[[2023,10,10]],"date-time":"2023-10-10T17:01:52Z","timestamp":1696957312000},"page":"3299-3309","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Functional similarity of ABP 959 and eculizumab in simulated serum models of aHUS and NMOSD"],"prefix":"10.1007","volume":"102","author":[{"given":"Helen J.","family":"McBride","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ashley","family":"Frazer-Abel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sandra","family":"Thiemann","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sonya G.","family":"Lehto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katariina M.","family":"Hutterer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jennifer","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2023,10,10]]},"reference":[{"key":"5439_CR1","unstructured":"Alexion Pharmaceuticals Inc. (2015) Soliris (eculizumab): US prescribing information. https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2017\/125166s422lbl.pdf. Accessed 6 July 2023"},{"key":"5439_CR2","unstructured":"Alexion Europe SAS. (2017) Soliris (eculizumab): summary of product characteristics. http:\/\/www.ema.europa.eu\/docs\/en_GB\/document_library\/EPAR_-_Product_Information\/human\/000791\/WC500054208.pdf. Accessed 6 July 2023"},{"key":"5439_CR3","unstructured":"US Food and Drug Administration (2023)\u00a0Developing products for rare diseases and conditions. Orphan drug designations and approvals. https:\/\/www.accessdata.fda.gov\/scripts\/opdlisting\/oopd\/listResult.cfm. Accessed 6 Jul 2023"},{"key":"5439_CR4","unstructured":"European Medicines Agency Public Assessment Report (EPAR). (2019) Soliris (eculizumab). https:\/\/www.ema.europa.eu\/documents\/overview\/soliris-epar-medicine-overview_en.pdf. Accessed 6 July 2023"},{"issue":"25","key":"5439_CR5","doi-asserted-by":"publisher","first-page":"6786","DOI":"10.1182\/blood-2011-02-333997","volume":"117","author":"RJ Kelly","year":"2011","unstructured":"Kelly RJ, Hill A, Arnold LM et al (2011) Long-term treatment with eculizumab in paroxysmal nocturnal hemoglobinuria: sustained efficacy and improved survival. Blood 117(25):6786\u20136792. https:\/\/doi.org\/10.1182\/blood-2011-02-333997","journal-title":"Blood"},{"issue":"2","key":"5439_CR6","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1212\/WNL.0000000000001729","volume":"85","author":"DM Wingerchuk","year":"2015","unstructured":"Wingerchuk DM, Banwell B, Bennett JL et al (2015) International consensus diagnostic criteria for neuromyelitis optica spectrum disorders. Neurology 85(2):177\u2013189. https:\/\/doi.org\/10.1212\/WNL.0000000000001729","journal-title":"Neurology"},{"issue":"4","key":"5439_CR7","doi-asserted-by":"publisher","first-page":"579","DOI":"10.1016\/j.cll.2019.07.006","volume":"39","author":"M Ling","year":"2019","unstructured":"Ling M, Murali M (2019) Analysis of the complement system in the clinical immunology laboratory. Clin Lab Med 39(4):579\u2013590. https:\/\/doi.org\/10.1016\/j.cll.2019.07.006","journal-title":"Clin Lab Med"},{"issue":"3","key":"5439_CR8","doi-asserted-by":"publisher","first-page":"1305","DOI":"10.4049\/jimmunol.176.3.1305","volume":"176","author":"JM Thurman","year":"2006","unstructured":"Thurman JM, Holers VM (2006) The central role of the alternative complement pathway in human disease. J Immunol 176(3):1305\u20131310. https:\/\/doi.org\/10.4049\/jimmunol.176.3.1305","journal-title":"J Immunol"},{"key":"5439_CR9","unstructured":"U. S. Food and Drug Administration (2018) Biosimilars action plan: Balancing Innovation and Competition. https:\/\/www.fda.gov\/media\/114574\/download. Accessed 6 July 2023"},{"key":"5439_CR10","doi-asserted-by":"crossref","unstructured":"Mulcahy AW, Hlavka JP, Case SR (2017) Biosimilar cost savings in the United States: Initial experience and future potential. Santa Monica, CA: RAND Corporation, 2017. https:\/\/www.rand.org\/pubs\/perspectives\/PE264.html. Accessed 6 July 2023","DOI":"10.7249\/PE264"},{"key":"5439_CR11","doi-asserted-by":"publisher","unstructured":"Hutterer KM, Ip A, Kuhns S et al (2021) Analytical similarity assessment of ABP 959 in comparison with eculizumab reference product. BioDrugs Sep;35(5):563\u2013577. https:\/\/doi.org\/10.1007\/s40259-021-00492-9","DOI":"10.1007\/s40259-021-00492-9"},{"key":"5439_CR12","doi-asserted-by":"crossref","unstructured":"Kulasekararaj A, Lanza F, Arvanitakis A et al (2022) Efficacy and safety of biosimilar candidate ABP 959 as compared with eculizumab reference product in paroxysmal nocturnal hemoglobinuria. Presented at 64th ASH Annual Meeting and Exposition, Dec 10 - 13, New Orleans, Louisiana","DOI":"10.1182\/blood-2022-166722"},{"issue":"1","key":"5439_CR13","doi-asserted-by":"publisher","first-page":"66","DOI":"10.1111\/ejh.13411","volume":"105","author":"V Chow","year":"2020","unstructured":"Chow V, Pan J, Chien D et al (2020) A randomized, double-blind, single-dose, three-arm, parallel group study to determine pharmacokinetic similarity of ABP 959 and eculizumab (Soliris\u00ae) in healthy male subjects. Eur J Haematol 105(1):66\u201374. https:\/\/doi.org\/10.1111\/ejh.13411","journal-title":"Eur J Haematol"},{"key":"5439_CR14","unstructured":"U. S. Food and Drug Administration (2016) Clinical Pharmacology Data to Support a Demonstration of Biosimilarity to a Reference Product. Guidance for Industry. https:\/\/www.fda.gov\/media\/88622\/download. Accessed 6 July 2023"},{"issue":"12","key":"5439_CR15","doi-asserted-by":"publisher","first-page":"2180","DOI":"10.1681\/ASN.2010030315","volume":"21","author":"MA Dragon-Durey","year":"2010","unstructured":"Dragon-Durey MA, Sethi SK et al (2010) Clinical features of anti-factor H autoantibody-associated hemolytic uremic syndrome. J Am Soc Nephrol 21(12):2180\u20132187. https:\/\/doi.org\/10.1681\/ASN.2010030315","journal-title":"J Am Soc Nephrol"},{"issue":"7","key":"5439_CR16","doi-asserted-by":"publisher","first-page":"3528","DOI":"10.4049\/jimmunol.1200679","volume":"189","author":"C Blanc","year":"2012","unstructured":"Blanc C, Roumenina LT, Ashraf Y et al (2012) Overall neutralization of complement factor H by autoantibodies in the acute phase of the autoimmune form of atypical hemolytic uremic syndrome. J Immunol 189(7):3528\u20133537. https:\/\/doi.org\/10.4049\/jimmunol.1200679","journal-title":"J Immunol"},{"issue":"2","key":"5439_CR17","doi-asserted-by":"publisher","first-page":"127","DOI":"10.1111\/sji.12132","volume":"79","author":"H Wang","year":"2014","unstructured":"Wang H, Wang K, Wang C et al (2014) Increased soluble C5b\u20139 in CSF of neuromyelitis optica. Scand J Immunol 79(2):127\u2013130","journal-title":"Scand J Immunol"},{"key":"5439_CR18","first-page":"133","volume-title":"Experimental immunochemistry, R","author":"MM Mayer","year":"1967","unstructured":"Mayer MM (1967) Complement and complement fixation. In: Kabat EA, Mayer MM (eds) Experimental immunochemistry, R, 2nd edn. Thomas, Springfield, pp 133\u2013240","edition":"2"},{"key":"5439_CR19","doi-asserted-by":"publisher","unstructured":"Giclas PC (2001) Classical pathway evaluation. Curr Protoc Immunol Chapter 13:Unit 13.1. https:\/\/doi.org\/10.1002\/0471142735.im1301s09","DOI":"10.1002\/0471142735.im1301s09"},{"issue":"1","key":"5439_CR20","doi-asserted-by":"publisher","first-page":"348","DOI":"10.4049\/jimmunol.113.1.348","volume":"113","author":"TA Platts-Mills","year":"1974","unstructured":"Platts-Mills TA, Ishizaka K (1974) Activation of the alternate pathway of human complements by rabbit cells. J Immunol 113(1):348\u2013358","journal-title":"J Immunol"},{"key":"5439_CR21","unstructured":"US Food and Drug Administration (2018) Bioanalytical method validation.\u00a0https:\/\/www.fda.gov\/files\/drugs\/published\/Bioanalytical-Method-Validation-Guidance-for-Industry.pdf. Accessed 6 Jul 2023"},{"issue":"4","key":"5439_CR22","doi-asserted-by":"publisher","first-page":"354","DOI":"10.1097\/00126334-200304010-00002","volume":"32","author":"L Heggelund","year":"2003","unstructured":"Heggelund L, Mollnes TE, Ueland T et al (2003) Mannose-binding lectin in HIV infection: relation to disease progression and highly active antiretroviral therapy. J Acquir Immune Defic Syndr 32(4):354\u2013356. https:\/\/doi.org\/10.1097\/00126334-200304010-00002","journal-title":"J Acquir Immune Defic Syndr"},{"issue":"11","key":"5439_CR23","doi-asserted-by":"publisher","first-page":"655","DOI":"10.1016\/s0161-5890(02)00254-7","volume":"39","author":"A Roos","year":"2003","unstructured":"Roos A, Bouwman LH, Munoz J (2003) Functional characterization of the lectin pathway of complement in human serum. MoI Immunol 39(11):655\u2013668. https:\/\/doi.org\/10.1016\/s0161-5890(02)00254-7","journal-title":"MoI Immunol"},{"issue":"6","key":"5439_CR24","first-page":"982","volume":"10","author":"M Kirschfink","year":"2003","unstructured":"Kirschfink M, Mollnes TE (2003) Modern complement analysis. Clin Diagn Lab Immunol 10(6):982\u2013989","journal-title":"Clin Diagn Lab Immunol"},{"key":"5439_CR25","doi-asserted-by":"publisher","unstructured":"Harder MJ, Kuhn N, Schrezenmeier H, Schmidt CQ et al (2017) Incomplete inhibition by eculizumab: mechanistic evidence for residual C5 activity during strong complement activation. Blood 129(8):970-980.\u00a0https:\/\/doi.org\/10.1182\/blood-2016-08-732800","DOI":"10.1182\/blood-2016-08-732800"},{"issue":"6","key":"5439_CR26","doi-asserted-by":"publisher","first-page":"982","DOI":"10.1128\/CDLI.10.6.982-989.2003","volume":"10","author":"M Kirschfink","year":"2003","unstructured":"Kirschfink M, Mollnes TE (2003) Modern complement analysis. Clin Diagn Lab Immunol 10(6):982\u2013989. https:\/\/doi.org\/10.1128\/CDLI.10.6.982-989.2003","journal-title":"Clin Diagn Lab Immunol"},{"issue":"4","key":"5439_CR27","doi-asserted-by":"publisher","first-page":"773","DOI":"10.1002\/ajmg.a.38413","volume":"176","author":"L Kempf","year":"2018","unstructured":"Kempf L, Goldsmith JC, Temple R (2018) Challenges of developing and conducting clinical trials in rare disorders. Am J Med Genet A 176(4):773\u2013783. https:\/\/doi.org\/10.1002\/ajmg.a.38413","journal-title":"Am J Med Genet A"},{"issue":"4","key":"5439_CR28","doi-asserted-by":"publisher","first-page":"e110","DOI":"10.1212\/NXI.0000000000000110","volume":"2","author":"A Zekeridou","year":"2015","unstructured":"Zekeridou A, Lennon VA (2015) Aquaporin-4 autoimmunity. Neurol Neuroimmunol Neuroinflamm 2(4):e110. https:\/\/doi.org\/10.1212\/NXI.0000000000000110","journal-title":"Neurol Neuroimmunol Neuroinflamm"},{"issue":"6","key":"5439_CR29","doi-asserted-by":"publisher","first-page":"1205","DOI":"10.1080\/19420862.2015.1086049","volume":"7","author":"P Gatault","year":"2015","unstructured":"Gatault P, Brachet G, Ternant D et al (2015) Therapeutic drug monitoring of eculizumab: rationale for an individualized dosing schedule. MAbs 7(6):1205\u20131211. https:\/\/doi.org\/10.1080\/19420862.2015.1086049","journal-title":"MAbs"},{"key":"5439_CR30","unstructured":"Association for Accessible Medicines (2021) The U. S. Generic Drug & Biosimilar Medicines Savings Report. https:\/\/accessiblemeds.org\/sites\/default\/files\/2021-10\/AAM-2021-US-Generic-Biosimilar-Medicines-Savings-Report-web.pdf. Accessed 6 July 2023"},{"issue":"1","key":"5439_CR31","first-page":"105","volume":"21","author":"D Tichaczek-Goska","year":"2012","unstructured":"Tichaczek-Goska D (2012) Deficiencies and excessive human complement system activation in disorders of multifarious etiology. Adv Clin Exp Med 21(1):105\u2013114","journal-title":"Adv Clin Exp Med"}],"container-title":["Annals of Hematology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00277-023-05439-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00277-023-05439-4\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00277-023-05439-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,11]],"date-time":"2023-11-11T05:05:55Z","timestamp":1699679155000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00277-023-05439-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,10,10]]},"references-count":31,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2023,12]]}},"alternative-id":["5439"],"URL":"https:\/\/doi.org\/10.1007\/s00277-023-05439-4","relation":{},"ISSN":["0939-5555","1432-0584"],"issn-type":[{"value":"0939-5555","type":"print"},{"value":"1432-0584","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,10,10]]},"assertion":[{"value":"3 April 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"31 August 2023","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 October 2023","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"This article does not contain any studies with human participants or animals performed by any of the authors.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}},{"value":"ST, SL, KH, and JL are employees and stockholders of Amgen, Inc. HM was an employee and stockholder at the time experiments were conducted. AFA is a consultant for Alexion, BioCryst, CSL Behring, Ionis Pharmaceuticals, Regeneron; this work was conducted through fee-for-service with Amgen Inc.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}