Ravulizumab Shows Favorable Survival and Improves Clinical Markers in Children With HSCT ‐ TMA : Results of a Phase 3 Trial

Hematopoietic stem cell transplantation‐associated thrombotic microangiopathy (HSCT‐TMA) is a rare, life‐threatening complication that can lead to multiorgan failure and death. The ALXN1210‐TMA‐314 global, Phase 3, open‐label, single‐arm trial evaluated ravulizumab, a C5 inhibitor, for treatment of HSCT‐TMA in children (NCT04557735). Eligible participants aged ≥ 28 days to < 18 years had HSCT‐TMA within 12 months from HSCT, which persisted for ≥ 72 h despite initial management. Participants received weight‐based ravulizumab plus best supportive care during the 26‐week treatment period, followed by a 26‐week follow‐up period. The protocol‐defined primary endpoint was complete TMA response during the treatment period. Key secondary endpoints included individual TMA response components (proteinuria, platelets, and lactate dehydrogenase/schistocytes), overall survival (OS), and safety. Of 41 enrolled participants (mean age, 7.6 years; 51.2% female), 28 (68.3%) completed treatment, and 24 (58.5%) completed the study. Through the treatment period, 7 (17.1%) participants achieved complete TMA response, and 22 (53.7%) achieved partial TMA response; 29 (70.7%) participants achieved improvement in ≥ 1 TMA response component. Estimated OS was 92.6% at Day 100, 87.2% at Week 26, and 73.4% at Week 52. During treatment, a low incidence of serious TEAEs was assessed by investigators as related to ravulizumab (3 participants, 7.3%); no new safety signals were identified. No meningococcal infections were reported. In this global Phase 3 trial in children with HSCT‐TMA, ravulizumab treatment resulted in excellent OS and normalization of early laboratory markers of TMA in many patients.