Ravulizumab for the treatment of paroxysmal nocturnal hemoglobinuria

Introduction: Eculizumab, which is indicated to treat patients with paroxysmal nocturnal hemoglobinuria (PNH), is a life-changing, life-saving therapy that decreases intravascular hemolysis and thrombosis and improves survival. Some eculizumab-treated patients, however, experience breakthrough hemolysis; and overall, the burden of the treatment schedule (intravenous infusions every 2 weeks) is substantial. Ravulizumab is a long-acting, second-generation complement component 5 (C5) inhibitor that is administered intravenously every 8 weeks. It is approved in the United States (December 2018), Japan (June 2019), Europe (July 2019), and Canada and Brazil (September 2019). Areas covered: This article reviews data presented in journal articles identified on Medline/PubMed, abstracts presented at hematology meetings, and information posted on ClinicalTrials.gov and Alexion.com. Emphasis is placed on the non-inferiority of ravulizumab compared to eculizumab and the advantages of the 8-week, weight-based, dosing regimen. Expert opinion: In phase 3 trials, ravulizumab has been shown to be as safe and efficacious as eculizumab, to be associated numerically with lower rates of breakthrough hemolysis (p for non-inferiority <0.0004), and to be preferred over eculizumab by most patients. Ravulizumab is likely to replace eculizumab as the first-line treatment for PNH both in patients who are naive to eculizumab treatment and in patients who are clinically stable on eculizumab.