Ravulizumab in Atypical Hemolytic Uremic Syndrome: An Analysis of 2-Year Efficacy and Safety Outcomes in 2 Phase 3 Trials
Bradley P. Dixon, David Kavanagh, Alvaro Domingo Madrid Aris, Brigitte Adams, Hee Gyung Kang, Edward Wang, Katherine Garlo, Masayo Ogawa, Praveen K. Amancha, S. Chakravarty, Nils Heyne, Seong Heon Kim, Spero Cataland, Sung‐Soo Yoon, Yoshitaka Miyakawa, Yosu Luque, Melissa Muff‐Luett, Kazuki Tanaka, Larry A. Greenbaum
Abstract
Rationale & ObjectiveAtypical hemolytic uremic syndrome (aHUS) is a rare form of thrombotic microangiopathy (TMA) caused by complement dysregulation. Ravulizumab is a complement C5 inhibitor (C5i) approved for the treatment of aHUS. This analysis assessed long-term outcomes of ravulizumab in adults and pediatric patients with aHUS.Study DesignThis analysis reports 2-year data from two phase 3, single-arm studies.Setting & ParticipantsOne study included C5i-naive adults (NCT02949128) and the other included two cohorts of pediatric patients (C5i-naive and those who switched to ravulizumab from eculizumab [pediatric switch patients]; NCT03131219).Exposure(s)Patients received intravenous ravulizumab every 4–8 weeks, with the dose depending on body weight.OutcomesThe primary endpoint in the studies of C5i-naive patients was complete TMA response, which consisted of platelet count normalization, lactate dehydrogenase normalization, and ≥25% improvement in serum creatinine from baseline, at two consecutive assessments at least 4 weeks apart.Analytical ApproachAll analyses used descriptive statistics. No formal statistical comparisons were performed.ResultsIn total, 86 and 92 patients were included in efficacy and safety analyses, respectively. Complete TMA response rates over 2 years were 61% and 90% in C5i-naive adults and pediatric patients, respectively. The median increase in eGFR from baseline was maintained over 2 years in C5i-naive adults (35 mL/min/1.73m2) and pediatric patients (82.5 mL/min/1.73m2). Most adverse events and serious adverse events occurred during the first 26 weeks. No meningococcal infections were reported. Improvement in the Functional Assessment of Chronic Illness Therapy – Fatigue score achieved by 26 weeks was maintained over 2 years.LimitationsLimitations were the small sample of pediatric switch patients and limited availability of genetic data.ConclusionsLong-term treatment with ravulizumab is well tolerated and associated with improved hematological and renal parameters and quality of life in adults and pediatric patients with aHUS.