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Danicopan: an oral complement factor D inhibitor for paroxysmal nocturnal hemoglobinuria
Risitano, Antonio M; Kulasekararaj, Austin G; Lee, Jong Wook; Maciejewski, Jaroslaw P; Notaro, Rosario; Brodsky, Robert; Huang, Mingjun; Geffner, Michael; Browett, Peter.
Afiliación
  • Risitano AM; Federico II University of Naples, Naples, Italy and AORN Moscati, Avellino. amrisita@unina.it.
  • Kulasekararaj AG; King's College Hospital-NHS Foundation Trust, NIHR/Wellcome King's Clinical Research Facility, London, UK and King's College London, London.
  • Lee JW; Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul.
  • Maciejewski JP; Cleveland Clinic, Cleveland, OH.
  • Notaro R; Core Research Laboratory, Istituto per lo Studio, la Prevenzione e la Rete Oncologica (ISPRO), Firenze, Italy; Azienda Ospedaliera-Universitaria Careggi, Firenze.
  • Brodsky R; Johns Hopkins University School of Medicine, Baltimore, MD.
  • Huang M; Achillion, Inc., A Subsidiary of Alexion Pharmaceuticals, Inc., New Haven, CT, USA; Alexion Pharmaceuticals, New Haven CT.
  • Geffner M; Achillion Inc., A Subsidiary of Alexion Pharmaceuticals, Inc., Blue Bell, PA.
  • Browett P; University of Auckland, Auckland.
Haematologica ; 106(12): 3188-3197, 2021 12 01.
Article en En | MEDLINE | ID: mdl-33121236
Paroxysmal nocturnal hemoglobinuria (PNH) is characterised by complement-mediated intravascular hemolysis (IVH) due to absence of complement regulators CD55 and CD59 on affected erythrocytes. Danicopan is a first-in-class oral proximal, complement alternative pathway factor D (FD) inhibitor. Therapeutic FD inhibition was designed to control IVH and prevent C3-mediated extravascular hemolysis (EVH). In this open-label, phase 2, dose-finding trial, 10 untreated hemolytic PNH patients received danicopan monotherapy (100-200 mg thrice daily). Endpoints included change in lactate dehydrogenase (LDH) at day 28 (primary) and day 84 and hemoglobin. Safety, pharmacokinetics/pharmacodynamics, and patient-reported outcomes were measured. Ten patients reached the primary endpoint; two later discontinued: one for a serious adverse event (elevated aspartate aminotransferase/alanine aminotransferase coincident with breakthrough hemolysis, resolving without sequelae) and one for personal reasons unrelated to safety. Eight patients completed treatment. IVH was inhibited, demonstrated by mean decreased LDH (5.7 times upper limit of normal [ULN] at baseline vs 1.8 times ULN [day 28] and 2.2 times ULN [day 84]; both p.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Factor D del Complemento / Hemoglobinuria Paroxística Límite: Humans Idioma: En Revista: Haematologica Año: 2021 Tipo del documento: Article

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Factor D del Complemento / Hemoglobinuria Paroxística Límite: Humans Idioma: En Revista: Haematologica Año: 2021 Tipo del documento: Article