The complement C5 inhibitor crovalimab in paroxysmal nocturnal hemoglobinuria
| Autor: | Sung Soo Yoon, Hubert Schrezenmeier, Jin Seok Kim, Simona Sica, Kensuke Usuki, Juliette Soret, Jens Panse, Alexandre Sostelly, Junichi Nishimura, Flore Sicre de Fontbrune, Marta Biedzka-Sarek, Brittany Gentile, Judith Anzures-Cabrera, Yoshikazu Ito, Régis Peffault de Latour, Barbara Klughammer, Christoph Bucher, Satoshi Ichikawa, Gregor Jordan, Zsolt Nagy, Andreas Dieckmann, Miklos Egyed, Angelika Jahreis, Alexander Röth, James Higginson, Haruhiko Ninomiya, Kenji Shinomiya, Júlia Gaál-Weisinger |
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| Rok vydání: | 2020 |
| Předmět: |
Clinical Trials and Observations
Immunology Hemoglobinuria Paroxysmal Medizin CD59 Antigens Pharmacology Biochemistry Pharmacokinetics the complement C5 inhibitor crovalimab in paroxysmal nocturnal hemoglobinuria medicine Humans Complement component 5 biology business.industry Complement C5 Cell Biology Hematology Eculizumab medicine.disease Complement system Settore MED/15 - MALATTIE DEL SANGUE Complement Inactivating Agents Pharmacodynamics biology.protein Paroxysmal nocturnal hemoglobinuria Hemoglobinuria Antibody business medicine.drug |
| Zdroj: | Blood. 135:912-920 |
| ISSN: | 1528-0020 0006-4971 |
| DOI: | 10.1182/blood.2019003399 |
| Popis: | Complement 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 |
| Databáze: | OpenAIRE |
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