Evaluating ravulizumab for the treatment of children and adolescents with paroxysmal nocturnal hemoglobinuria

Introduction Paroxysmal nocturnal hemoglobinuria (PNH) is a rare acquired clonal stem cell disease harvesting a somatic mutation in the phosphatidylinositol glycan class A (PIG-A) gene. This mutation results in a deficiency in cell membrane complement regulators leading to activation of the terminal complement pathway, clinically presenting as hemolytic anemia and thrombosis, and frequently associated with bone marrow failure. This condition was historically managed with supportive care and bone marrow transplant. Areas Covered This paper will review primary data on the pharmacology, efficacy, and safety of ravulizumab in the pediatric/adolescent population gathered from literature search from PubMed, abstracts from annual meetings, and medication package inserts. Eligible clinical trials identified on the clinicaltrials.gov website are also briefly discussed. Expert Opinion The discovery of eculizumab, a monoclonal antibody against complement protein 5, has revolutionized the PNH landscape, with decreased hemolysis and risk of thrombosis, improved quality-of-life, and has become the standard of care. Ravulizumab, a longer-acting C5-inhibitor with 4 times the half-life of eculizumab, was recently approved for pediatric patients with PNH. Ravulizumab is effective, safe, and has the potential to improve quality of life further. In addition, ongoing clinical trials using second-generation complement inhibitors may provide promising new interventions in PNH.