Efficacy and safety of eculizumab in children and adolescents with paroxysmal nocturnal hemoglobinuria

Background Paroxysmal nocturnal hemoglobinuria (PNH) is rare in children, but represents a similarly serious and chronic condition as in adults. Children with PNH frequently experience complications of chronic hemolysis, recurrent thrombosis, marrow failure, serious infections, abdominal pain, chronic fatigue, and decreased quality of life with reduced survival. The terminal complement inhibitor eculizumab is proven to be effective and safe in adults and approved by the FDA for treatment of PNH. Procedure This 12‐week, open‐label, multi‐center phase I/II study evaluated pharmacokinetics, pharmacodynamics, efficacy, and safety in seven children with PNH 11–17 years of age. Eculizumab was intravenously administered at 600 mg weekly for 4 weeks, 900 mg in week 5, and 900 mg every 2 weeks thereafter (http://clinicaltrials.gov NCT00867932). Results Eculizumab therapy resulted in complete and sustained inhibition of hemolysis in all participants with a reduction of lactate dehydrogenase to normal levels. All hematological parameters stabilized. No definitive, study drug‐related adverse events were observed. Only one severe SAE of hospitalization due to aplastic anemia occurred, which was not study drug‐related. Conclusion Eculizumab appears to be a safe and effective therapy for children with PNH. Pediatr Blood Cancer 2014;61:1544–1550. © 2014 Wiley Periodicals, Inc.