Ravulizumab in Pregnancy Shows No New Safety Signals in Global Analysis

A rare bit of good news has emerged for women living with some of medicine’s most challenging immune disorders: one of the newest drugs in their arsenal appears to be holding up well during pregnancy. A global pharmacovigilance analysis published in the journal Advances in Therapy has compiled real-world safety data on ravulizumab, a second-generation complement inhibitor, in pregnant patients across four rare diseases. Drawing on more than eight years of worldwide post-marketing surveillance and 48,345 patient-years of cumulative drug exposure, the analysis identified 354 reported pregnancies with at least one documented dose of ravulizumab. Among the cases with known outcomes, roughly two-thirds ended in live births, and the investigators found no unexpected safety signals beyond those already established for the older drug eculizumab, from which ravulizumab was engineered. For a patient population that was once routinely advised to avoid pregnancy altogether, the findings represent a meaningful step forward, though researchers are quick to caution that the evidence base remains incomplete and that a dedicated pregnancy registry is now underway to fill the gaps.

To understand why this analysis matters, it helps to grasp what these drugs actually do. Ravulizumab is a monoclonal antibody that blocks the terminal pathway of the complement system, a branch of innate immunity that normally helps destroy pathogens and damaged cells. In pregnancy, complement activity is tightly choreographed to protect the developing placenta while maintaining immunological tolerance between mother and fetus. But in a group of rare, complement-mediated disorders, this system turns against the body’s own tissues. In paroxysmal nocturnal hemoglobinuria, or PNH, uncontrolled complement activation destroys red blood cells and drives life-threatening blood clots. In atypical hemolytic uremic syndrome, or aHUS, it attacks the small vessels of the kidneys. In generalized myasthenia gravis and neuromyelitis optica spectrum disorder, antibody-driven complement activation damages the neuromuscular junction and the optic nerves and spinal cord, respectively. When pregnancy superimposes its own physiological upheaval on these already volatile conditions, the result can be disease flares, hemolysis, thrombosis, kidney failure, and serious fetal complications.

The historical numbers explain why pregnancy was once actively discouraged in these patients. Before complement blockers arrived, maternal mortality in pregnant women with PNH ranged from 8 to 21 percent, driven largely by postpartum thrombosis, with fetal mortality estimated at 4 to 9 percent. In aHUS, maternal mortality was reported at around 5 percent, and women faced high risks of progressing to chronic kidney disease, end-stage kidney disease, and dialysis dependence, alongside fetal dangers including intrauterine death, growth restriction, low birth weight, and prematurity. In myasthenia gravis, at least one-third of patients experience symptom worsening during pregnancy, particularly in the first trimester and after delivery. And in NMOSD, pregnancy is associated with increased relapse risk and elevated rates of miscarriage, reported at 22.6 percent, along with premature delivery and preeclampsia. Against this backdrop, the arrival of eculizumab, the first terminal complement C5 inhibitor approved in the United States in 2007, transformed the calculus, allowing many women with these disorders to carry pregnancies safely for the first time.

Ravulizumab, approved by the FDA in 2018, was engineered from eculizumab with an improved pharmacokinetic profile that allows immediate, complete, and sustained terminal complement inhibition with much longer intervals between doses. That pharmacological advantage, however, came with an evidentiary disadvantage: because the drug had been on the market for a shorter time, its pregnancy safety data were limited largely to scattered case reports and small case series. The new analysis, conducted by researchers at Alexion, AstraZeneca Rare Disease, set out to close that gap by mining the company’s global pharmacovigilance database, which collects adverse event reports from solicited sources such as patient support programs and disease registries, spontaneous reports from healthcare professionals, patients, and regulators, and structured literature searches. Every pregnancy case in which the mother received at least one dose of ravulizumab was captured, regardless of how complete the report was, and duplicate reports of the same pregnancy were consolidated to avoid double counting.

The dataset spans 25 countries across Australia, the Americas, Europe, the Middle East, and Asia-Pacific, covering the period from December 21, 2018, when ravulizumab was first authorized, through December 31, 2025. Of the 354 reported pregnancy cases, the largest group involved women with PNH, at 160 cases, followed by aHUS with 72, generalized myasthenia gravis with 38, and NMOSD with 34; in 45 cases the underlying indication was not reported, and five involved other conditions. Pregnancy outcomes were available for only 106 of these cases, or 29.9 percent, with the remainder unavailable because of ongoing pregnancies, reporting lag, or data and privacy limitations. Among those 106 cases with known outcomes, there were 68 live births, or 64.2 percent, 29 spontaneous abortions, or 27.4 percent, three fetal deaths, or 2.8 percent, and six elective terminations, or 5.7 percent. Most of the outcome-documented cases came from the United States, followed by Japan, Germany, and the United Kingdom.

Exposure patterns varied considerably. Among cases with outcome data, only 17 percent involved ravulizumab exposure throughout the entire pregnancy, while 24.5 percent involved a switch from ravulizumab to eculizumab at some point during gestation, and in 58.5 percent of cases the exposure details were incomplete. To sharpen the picture, the researchers examined a nested subset of 44 post-marketing cases with detailed exposure information and known outcomes. In this subset, live births accounted for 72.7 percent of pregnancies, spontaneous abortions for 25 percent, and one elective termination. The live births included 17 pregnancies in which the mother received ravulizumab through all three trimesters, three in which exposure continued beyond 12 weeks but stopped before delivery, and 11 with first-trimester-only exposure. Because ravulizumab has a long half-life, the authors note, even limited early exposure is clinically relevant, since the drug persists in circulation long after the last infusion.

Perhaps the most striking finding is what did not appear. Among the detailed subset of 44 cases, no maternal deaths were reported, and there were no events suggesting inadequate disease control, such as major thrombotic events, in women receiving ravulizumab during pregnancy. Reported complications, which included thrombocytopenia, renal failure, pre-eclampsia, anemia, breakthrough hemolysis, one myasthenic crisis in a patient with myasthenia gravis, and assorted comorbidities such as chronic kidney disease and cirrhosis, reflect the serious underlying illnesses of the patient population rather than a clear drug-specific pattern. The live birth rate in the full outcome-documented cohort, 64.2 percent, compares favorably with the roughly 70 percent live birth rate reported in a ten-year pharmacovigilance analysis of eculizumab in pregnant women with PNH or aHUS, and the fetal death rate of 2.8 percent was actually lower than the 3.5 percent observed with eculizumab. The authors acknowledge that the spontaneous abortion figure may look elevated at first glance, but they attribute this largely to the small number of cases with available outcome data and note that the rate is similar to that seen in pregnancies complicated by other chronic illnesses.

The new analysis also dovetails with a growing body of clinical literature. A recent case series of 19 ravulizumab-exposed pregnancies reported favorable maternal and fetal outcomes, with every pregnancy ending in a live birth, and individual case reports have described positive outcomes in women with aHUS and NMOSD as well as PNH. One particularly intriguing report documented transplacental transfer of ravulizumab and neonatal complement inhibition in a pregnancy complicated by NMOSD, yet the infant showed no adverse effects. That observation raises questions that only systematic follow-up can answer, since fetal exposure to a complement-blocking antibody could in principle affect the newborn’s developing immune defenses, even when no immediate harm is evident. It is precisely these kinds of subtle, delayed effects that spontaneous pharmacovigilance reporting is least equipped to detect, which is why the authors and independent experts alike emphasize the need for prospective data.

That need is being addressed. Alexion has launched a global observational ravulizumab pregnancy registry, registered as NCT06312644, spanning Australia, France, Germany, Italy, South Korea, the United Kingdom, and the United States. The study enrolls women exposed to ravulizumab at any point from up to 40 weeks before conception through pregnancy or breastfeeding, and follows infants through the first 52 weeks of life, aiming to systematically capture maternal, fetal, and neonatal outcomes. Until those data mature, the current analysis offers a cautiously reassuring signal rather than a definitive verdict. The authors are candid about the limitations inherent to post-marketing surveillance: there are no patient-level identifiers, no comparator groups, no way to calculate true incidence rates, and no capacity for longitudinal follow-up, and reporting bias toward unfavorable outcomes may inflate apparent risks. Still, within those constraints, the message is consistent. Ravulizumab exposure during pregnancy, across more than 48,000 patient-years of global experience, has not produced any safety concerns beyond those already known for its predecessor, and the findings may help clinicians and patients navigate shared decisions about treatment during one of the most medically fraught journeys in modern medicine.

Subject of Research: Real-world pharmacovigilance assessment of ravulizumab safety during pregnancy in complement-mediated disorders

Article Title: Safety of Ravulizumab Use in Pregnancy: Insights from a Global Pharmacovigilance Analysis

Article References: Carrillo Infante, C., Mujeebuddin, A., Koneru, M., & Williams, C. (2026). Safety of Ravulizumab Use in Pregnancy: Insights from a Global Pharmacovigilance Analysis. Advances in Therapy. https://doi.org/10.1007/s12325-026-03816-9

Image Credits: AI Generated

DOI: 10.1007/s12325-026-03816-9

Keywords: ravulizumab, pregnancy, pharmacovigilance, complement C5 inhibitor, paroxysmal nocturnal hemoglobinuria, atypical hemolytic uremic syndrome, myasthenia gravis, neuromyelitis optica spectrum disorder, eculizumab, drug safety, real-world evidence, pregnancy outcomes