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

The numbers are striking. Among 54 patients followed for a median of 10 months, 98.1 percent achieved at least one lactate dehydrogenase value at or below 1.5 times the upper limit of normal, the standard biochemical signature that red-cell destruction has been brought to heel. Even more consequential for daily life, 85.2 percent reached hemoglobin concentrations of 120 grams per liter or higher, a threshold that generally marks the boundary between anemia and normal oxygen-carrying capacity. And in a finding that will resonate with every patient who has scheduled life around transfusion appointments, all 20 patients who were transfusion-dependent at the start of treatment became transfusion-independent.

To understand why those results matter, it helps to look at the molecular machinery involved. In PNH, a somatic mutation in the PIGA gene eliminates the glycosylphosphatidylinositol anchors that hold protective proteins such as CD55 and CD59 to the surface of blood cells. Without CD59, the membrane attack complex, a barrel-shaped assembly of complement proteins that punches lethal holes in cell membranes, forms freely on red cells, and chronic intravascular hemolysis follows. Free hemoglobin spills into the plasma, scavenges nitric oxide, and drives the smooth-muscle spasms, abdominal pain, erectile dysfunction, and pulmonary hypertension that make the disease so debilitating. The same uncontrolled complement activation consumes platelets’ protection and fuels the thromboses that historically made PNH one of the deadliest benign hematologic conditions.

The first generation of targeted therapy, the anti-C5 antibodies eculizumab and ravulizumab, transformed that prognosis by blocking the terminal step of the complement cascade. But C5 inhibition has a structural limitation: it stops the membrane attack complex while leaving the upstream alternative pathway running. Red cells coated with C3 fragments survive destruction in the bloodstream only to be cleared by macrophages in the spleen and liver, a process called extravascular hemolysis that keeps many patients anemic and transfusion-dependent. Roughly a quarter of patients on C5 inhibitors continue to require transfusions, and some experience breakthrough hemolysis when complement activation overwhelms the drug.

Iptacopan takes a different route. As a small-molecule inhibitor of factor B, it shuts down the alternative pathway at its point of amplification, upstream of both C3 opsonization and terminal complex formation. In theory, that should prevent intravascular hemolysis and the C3-coated red cells that fuel extravascular hemolysis, addressing the disease at a more fundamental level. The pivotal phase three APPOINT-PNH trial, which enrolled complement inhibitor-naive patients internationally, demonstrated exactly that, with most participants achieving hemoglobin normalization without transfusions and earning the drug regulatory approvals in the United States, Europe, and elsewhere as the first oral monotherapy for PNH.

What the new Chinese study adds is evidence from a real-world population outside the tightly controlled boundaries of a registration trial. The 54 patients, 17 of them women, had a median age of 38 years and ranged from 21 to 82, drawn from a network of hospitals spanning Beijing, Wuhan, Chengdu, Zhengzhou, Taiyuan, Kunming, and other cities. The investigators tracked clinical and laboratory indicators at one, three, and six months after starting iptacopan and through subsequent follow-up. Notably, the benefits held across disease subtypes: patients with classic hemolytic PNH and those with an aplastic anemia-PNH overlap syndrome, in which bone marrow failure compounds the hemolysis, showed no significant differences in their hemolytic parameters on treatment.

Safety, always the second half of the efficacy equation, was equally reassuring. The most common adverse events were headache and upper respiratory tract infection, each affecting 13 percent of patients. Breakthrough hemolysis, the feared scenario in which hemolysis resumes despite therapy, occurred in only 7.4 percent of the cohort. The study recorded no new thrombotic or microvascular events, no extravascular hemolysis, and, critically, no breakthrough infections with Neisseria meningitidis or Streptococcus pneumoniae, the encapsulated bacteria against which complement pathway blockade raises a well-known shield. Meningococcal infection is the reason all complement inhibitor users require vaccination and vigilance, and its complete absence in this cohort, while reassuring, underscores that the follow-up window remains relatively short.

The retrospective design carries inherent caveats that the authors and independent observers alike will emphasize. Without randomization or a control group, the study cannot exclude the influence of selection bias, and the median follow-up of 10 months, with a range of 6 to 18, leaves long-term durability, cumulative toxicity, and pregnancy outcomes open questions. Laboratory monitoring schedules varied across the many participating centers, and the analysis of patients who discontinued treatment or required dose adjustments will be scrutinized as the full paper circulates. Still, the consistency of the findings with the phase three data, in a health system and genetic background not represented in the original trials, strengthens the case that the drug’s benefits generalize.

For Chinese patients, the practical implications are immediate. Before factor B inhibitors, the standard of care in much of China, as in many middle-income countries, was limited by the cost and intravenous infrastructure demands of C5 monoclonal antibodies, leaving many patients managed with transfusions, iron supplementation, and anticoagulation alone. An oral agent that can be prescribed across a network of provincial hospitals, and that returned every transfusion-dependent patient in this cohort to transfusion independence, represents a meaningful shift in what standard care can look like outside major academic centers.

The broader scientific story is equally compelling. PNH was the first disease in which a clonal hematopoiesis was shown to be rescued not by eliminating the mutant clone but by pharmacologically disarming the selective pressure it exploited, a conceptual template now being applied across complement-mediated disorders, from IgA nephropathy to C3 glomerulopathy. Iptacopan’s real-world performance in China, with sustained hemolytic control, significant hemoglobin improvement, and a favorable safety profile, confirms that the alternative pathway is a druggable Achilles’ heel of this disease. As longer follow-up accumulates and prospective studies in additional populations mature, the question is shifting from whether oral factor B inhibition works to how best to sequence, monitor, and eventually tailor complement blockade to each patient’s biology, a question that the next decade of PNH research is now well positioned to answer.

Subject of Research: Real-world efficacy and safety of the oral complement factor B inhibitor iptacopan in Chinese patients with paroxysmal nocturnal hemoglobinuria

Article Title: Iptacopan treatment for chinese patients with hemolytic paroxysmal nocturnal hemoglobinuria (PNH): a multicenter retrospective study

Article References: Wang, L., Zhang, M., Chang, H., Zhou, H., Ma, S., Ma, Y., Miao, D., Zhou, Z., Jia, J., Zhang, R., Zhang, G., Liu, J., Zhu, Q., Yu, B., Wang, H., Hou, R., Ge, W., Wang, L., Lang, J., … Han, B. (2026). Iptacopan treatment for chinese patients with hemolytic paroxysmal nocturnal hemoglobinuria (PNH): a multicenter retrospective study. Annals of Hematology. https://doi.org/10.1007/s00277-026-07230-7

Image Credits: AI Generated

DOI: 10.1007/s00277-026-07230-7

Keywords: paroxysmal nocturnal hemoglobinuria, iptacopan, complement inhibitor, factor B, hemolysis, hemoglobin, transfusion independence, alternative pathway, breakthrough hemolysis, retrospective study, Annals of Hematology, China