Abstract
Introduction: Ravulizumab, a long-acting C5 complement inhibitor and second-generation analog of eculizumab, is approved for the treatment of hematologic and complement-mediated disorders including paroxysmal nocturnal hemoglobinuria (PNH) and atypical hemolytic uremic syndrome (aHUS) in adults and pediatric patients, as well as rare auto-immune diseases (generalized myasthenia gravis [gMG] and neuromyelitis optica spectrum disorder [NMOSD]) in adults. PNH and aHUS are disorders associated with high maternal and fetal morbidity in pregnancy. There are multiple reports on the use of eculizumab (approved for the same four indications) in pregnant patients where no safety signals have been observed. However, the safety profile of ravulizumab with respect to use during pregnancy and lactation, including its potential effects on fetal development and breastfed infants remain incomplete. This analysis aims to provide insights into pregnancy-related safety following ravulizumab exposure using data from global post-marketing surveillance.
Methods: Here, we analyze all pregnancy cases reported globally in the post-marketing setting of ravulizumab, with ≥1 documented dose of exposure. Data from both spontaneous and solicited cases recorded in the Alexion pharmacovigilance database from the initial market approval up to June 26, 2025 were included in the analysis. Descriptive statistics were used to summarize patient demographics, treatment patterns, and pregnancy outcomes.
Results: Among the 256 identified pregnancy cases with ≥1 dose of ravulizumab exposure, hematologic conditions represented a substantial proportion of underlying maternal diagnoses (PNH [n=117], aHUS [n=56]). Of the non-hematologic conditions, underlying maternal diagnosis included gMG (n=29) and NMOSD (n=12). Among 79 cases with data on pregnancy outcomes, the distribution of ravulizumab exposure included full-pregnancy exposure in 26.6%, ravulizumab to eculizumab switch during pregnancy in 26.6% and incomplete exposure details reported in 43.1%. Pregnancy outcomes included live births (n=51), spontaneous abortions (n=22), fetal deaths (n=3), and elective terminations (n=3). Moreover, in a subset of 38 pregnancies (PNH [n=19]) more detailed information was available on ravulizumab exposure. Maternal co-morbidities reported, predominantly in PNH, were aplastic anemia (n=4), Budd-Chiari syndrome (n=2), hypertension including gestational (n=3), and gestational diabetes (n=1). In this subset, 29 were live births (PNH [n=15]), of which, 16 had ravulizumab exposure throughout all trimesters, 3 had exposure beyond 12 weeks but discontinued prior to delivery, and 8 had exposure limited to the first trimester (≤12 weeks).
Conclusion: This analysis provides real-world insights on the use of ravulizumab in pregnancy and suggests no unexpected safety signals, similar to analyses on the use of eculizumab during pregnancy. These findings may inform clinical decision-making. As additional data are needed, a global observational study (NCT06312644) evaluating the safety of ravulizumab during pregnancy is currently ongoing.
