Ravulizumab in paroxysmal nocturnal hemoglobinuria: a profile of its use
- 26 Downloads
Ravulizumab (Ultomiris™) is a humanized monoclonal antibody that inhibits terminal complement C5, thereby reducing hemolysis, inflammation, and thrombosis in patients with paroxysmal nocturnal hemoglobinuria (PNH). Ravulizumab was developed by re-engineering eculizumab to create a longer-acting antibody, which allows an 8-weekly administration schedule instead of the 2-weekly schedule required with eculizumab. A single intravenous infusion of ravulizumab provides immediate and complete inhibition of serum free C5. With continued ravulizumab treatment, breakthrough hemolysis rates decrease as a result of eliminating free C5-associated breakthrough hemolysis. The efficacy of ravulizumab is noninferior to that of eculizumab, as determined in complement-inhibitor naive patients and those previously treated with eculizumab. Ravulizumab was generally well tolerated, with a generally comparable tolerability profile to that of eculizumab.
The manuscript was updated from Drugs 2019; 79(3):347–52 , and was reviewed by: Richard A. Wells, Department of Hematology/Oncology, Sunnybrook Health Sciences Centre, University of Toronto, ON, Canada; Jong Wook Lee, Department of Haematology, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea. During the peer review process, Alexion, the marketing-authorization holder of ravulizumab, was also offered an opportunity to provide a scientific accuracy review of their data. Changes resulting from comments received were made on the basis of scientific and editorial merit.
Compliance with ethical standards
The preparation of this review was not supported by any external funding.
Conflict of interest
K. McKeage and K.A. Lyseng-Williamson are employees of Adis International Ltd/Springer Nature and are responsible for the article content. K. McKeage declares no conflicts of interest. K.A. Lyseng-Williamson is the Editor of Drugs & Therapy Perspectives and has no other conflicts of interest to declare. The Editor of D&TP was not involved in any publishing decisions for the manuscript.
- 3.Sahin F, Akay OM, Ayer M, et al. Pesg PNH diagnosis, follow-up and treatment guidelines. Am J Blood Res. 2016;6(2):19–27.Google Scholar
- 4.Soliris® (eculizumab) injection for intravenous use: US prescribing information. Boston: Alexion Pharmaceuticals, Inc.; 2019.Google Scholar
- 5.Soliris (eculizumab) 300 mg concentrate for solution for infusion: EU summary of product characteristics. Rueil-Malmaison: Alexion Europe SAS; 2018.Google Scholar
- 7.Ultomiris™ (ravulizumab-cwvz) injection, for intravenous use: US prescribing information. Boston: Alexion Pharmaceuticals, Inc.; 2018.Google Scholar
- 8.Ultomiris (ravulizumab) 300 mg concentrate for solution for infusion: EU summary of product characteristics. Rueil-Malmaison: Alexion Europe SAS; 2019.Google Scholar
- 12.De Latour RP, Brodsky RA, Ortiz S, et al. Ravulizumab (ALXN1210) versus eculizumab in adults with paroxysmal nocturnal hemoglobinuria: pharmacokinetics and pharmacodynamics observed in two phase 3 randomized, multicenter studies (abstract). Blood. 2018;132(Suppl 1):626.Google Scholar
- 14.Weitz IC, Kulagin A, Nakao S, et al. A phase 3 study of ravulizumab (ALXN1210) versus eculizumab in adults with paroxysmal nocturnal hemoglobinuria naive to complement inhibitors: results of a subgroup analysis with patients stratified by baseline hemolysis level, transfusion history, and demographics (abstract). Blood. 2018;132(Suppl 1):627.Google Scholar