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The complement C5 inhibitor crovalimab in paroxysmal nocturnal hemoglobinuria

DC Field Value Language
dc.contributor.author김진석-
dc.date.accessioned2020-12-01T17:31:47Z-
dc.date.available2020-12-01T17:31:47Z-
dc.date.issued2020-03-
dc.identifier.issn0006-4971-
dc.identifier.urihttps://ir.ymlib.yonsei.ac.kr/handle/22282913/180314-
dc.description.abstractComplement C5 inhibition is the standard of care (SoC) for patients with paroxysmal nocturnal hemoglobinuria (PNH) with significant clinical symptoms. Constant and complete suppression of the terminal complement pathway and the high serum concentration of C5 pose challenges to drug development that result in IV-only treatment options. Crovalimab, a sequential monoclonal antibody recycling technology antibody was engineered for extended self-administered subcutaneous dosing of small volumes in diseases amenable for C5 inhibition. A 3-part open-label adaptive phase 1/2 trial was conducted to assess safety, pharmacokinetics, pharmacodynamics, and exploratory efficacy in healthy volunteers (part 1), as well as in complement blockade-naive (part 2) and C5 inhibitor-treated (part 3) PNH patients. Twenty-nine patients were included in part 2 (n = 10) and part 3 (n = 19). Crovalimab concentrations exceeded the prespecified 100-µg/mL level and resulted in complete and sustained terminal complement pathway inhibition in treatment-naive and C5 inhibitor-pretreated PNH patients. Hemolytic activity and free C5 levels were suppressed below clinically relevant thresholds (liposome assay <10 U/mL and <50 ng/mL, respectively). Safety was consistent with the known profile of C5 inhibition. As expected, formation of drug-target-drug complexes was observed in all 19 patients switching to crovalimab, manifesting as transient mild or moderate vasculitic skin reactions in 2 of 19 participants. Both events resolved under continued treatment with crovalimab. Subcutaneous crovalimab (680 mg; 4 mL), administered once every 4 weeks, provides complete and sustained terminal complement pathway inhibition in patients with PNH, warranting further clinical development-
dc.description.statementOfResponsibilityrestriction-
dc.languageEnglish-
dc.publisherAmerican Society of Hematology-
dc.relation.isPartOfBLOOD-
dc.rightsCC BY-NC-ND 2.0 KR-
dc.subject.MESHAdult-
dc.subject.MESHAged-
dc.subject.MESHAntibodies, Monoclonal / pharmacology-
dc.subject.MESHAntibodies, Monoclonal / therapeutic use*-
dc.subject.MESHBiomarkers-
dc.subject.MESHComplement C5 / antagonists & inhibitors*-
dc.subject.MESHComplement C5 / immunology-
dc.subject.MESHComplement Inactivating Agents / pharmacology-
dc.subject.MESHComplement Inactivating Agents / therapeutic use*-
dc.subject.MESHDrug Monitoring-
dc.subject.MESHFemale-
dc.subject.MESHHemoglobinuria, Paroxysmal / blood-
dc.subject.MESHHemoglobinuria, Paroxysmal / drug therapy*-
dc.subject.MESHHemoglobinuria, Paroxysmal / immunology-
dc.subject.MESHHumans-
dc.subject.MESHMale-
dc.subject.MESHMiddle Aged-
dc.subject.MESHQuality of Life-
dc.subject.MESHTreatment Outcome-
dc.titleThe complement C5 inhibitor crovalimab in paroxysmal nocturnal hemoglobinuria-
dc.typeArticle-
dc.contributor.collegeCollege of Medicine (의과대학)-
dc.contributor.departmentDept. of Internal Medicine (내과학교실)-
dc.contributor.googleauthorAlexander Röth-
dc.contributor.googleauthorJun-Ichi Nishimura-
dc.contributor.googleauthorZsolt Nagy-
dc.contributor.googleauthorJulia Gaàl-Weisinger-
dc.contributor.googleauthorJens Panse-
dc.contributor.googleauthorSung-Soo Yoon-
dc.contributor.googleauthorMiklos Egyed-
dc.contributor.googleauthorSatoshi Ichikawa-
dc.contributor.googleauthorYoshikazu Ito-
dc.contributor.googleauthorJin Seok Kim-
dc.contributor.googleauthorHaruhiko Ninomiya-
dc.contributor.googleauthorHubert Schrezenmeier-
dc.contributor.googleauthorSimona Sica-
dc.contributor.googleauthorKensuke Usuki-
dc.contributor.googleauthorFlore Sicre de Fontbrune-
dc.contributor.googleauthorJuliette Soret-
dc.contributor.googleauthorAlexandre Sostelly-
dc.contributor.googleauthorJames Higginson-
dc.contributor.googleauthorAndreas Dieckmann-
dc.contributor.googleauthorBrittany Gentile-
dc.contributor.googleauthorJudith Anzures-Cabrera-
dc.contributor.googleauthorKenji Shinomiya-
dc.contributor.googleauthorGregor Jordan-
dc.contributor.googleauthorMarta Biedzka-Sarek-
dc.contributor.googleauthorBarbara Klughammer-
dc.contributor.googleauthorAngelika Jahreis 19-
dc.contributor.googleauthorChristoph Bucher 17-
dc.contributor.googleauthorRégis Peffault de Latour 22 23-
dc.identifier.doi10.1182/blood.2019003399-
dc.contributor.localIdA01017-
dc.relation.journalcodeJ00341-
dc.identifier.eissn1528-0020-
dc.identifier.pmid31978221-
dc.identifier.urlhttps://ashpublications.org/blood/article/135/12/912/440744/The-complement-C5-inhibitor-crovalimab-in-
dc.contributor.alternativeNameKim, Jin Seok-
dc.contributor.affiliatedAuthor김진석-
dc.citation.volume135-
dc.citation.number12-
dc.citation.startPage912-
dc.citation.endPage920-
dc.identifier.bibliographicCitationBLOOD, Vol.135(12) : 912-920, 2020-03-
dc.identifier.rimsid67552-
dc.type.rimsART-
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers

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