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Treatment with the monoclonal antibody nipocalimab improved live birth outcomes and delayed or prevented fetal anemia or intrauterine transfusions in pregnancies at high risk for early-onset severe hemolytic disease of the fetus and newborn (HDFN), an open-label phase II study showed.

Among 13 pregnancies -- during which all mothers received intravenous nipocalimab -- live birth at 32 weeks' gestation or later without an intrauterine transfusion occurred in seven of them (54%, 95% CI 25-81), reported Kenneth Moise, Jr., MD, of Dell Children's Medical Center in Austin, Texas, and colleagues.

This was significantly higher than the 10% clinically meaningful difference from the historical benchmark of 0% (P<0.001), they noted in the .

Severe HDFN "results from maternal-fetal erythrocyte antigen incompatibility and transplacental transfer of maternal antierythrocyte antigen IgG alloantibodies, which cause fetal hemolytic anemia," Moise and colleagues wrote. "Early-onset severe HDFN ... occurring at 24 weeks' gestation or earlier, is associated with substantial fetal and neonatal morbidity and mortality."

Nipocalimab is an investigational neonatal Fc receptor (FcRn) blocker that aims to "inhibit alloantibody transfer to the fetus and to lower maternal IgG alloantibody titers," they wrote.

Historically, intrauterine transfusion of "compatible red cells for the treatment of severe HDFN was introduced into clinical practice more than 60 years ago," Moise told 番茄社区 in an email. "Some modification to the initial procedure occurred in the mid-1980s with the advent of the intravascular approach -- injecting red cells directly into the umbilical cord of the fetus under ultrasound guidance. Yet complications with the procedure, especially if performed before 24 weeks gestation, can lead to premature delivery and fetal death."

Moise added that the monoclonal antibody "may one day replace the need for intrauterine transfusions" if it's proven safe and effective in an ongoing randomized phase III trial.

Among the six pregnancies (46%) in which the primary endpoint was not met, fetal anemia leading to intrauterine transfusion occurred in five.

Three participants discontinued because of stopping criteria related to intrauterine transfusion, and two participants met stopping criteria because of adverse events (one case of grade 3 fetal anemia resulting in emergency delivery 2 weeks after the only intrauterine transfusion and one event of fetal demise within 1 day of the only intrauterine transfusion). The remaining participant discontinued due to a subchorionic hematoma and fetal growth restriction, but received intrauterine transfusions 4 weeks later.

A serious adverse event occurred in 42% of the 12 live births, and a severe adverse event occurred in 33%. Combined, 67% had a serious or severe adverse event, study authors said, noting these were "related to HDFN (jaundice, hyperbilirubinemia, or anemia), prematurity (respiratory distress), and a grade 3 low IgG level at birth in one neonate."

, Emeline Maisonneuve, MD, of Lausanne University Hospital in Switzerland, and colleagues said that, "[m]ore clinical data are needed to determine the role of nipocalimab as a secondary prevention option for high-risk early-onset severe HDFN and to identify and minimize its potential side effects."

"To determine the most effective dose and treatment duration while reducing neonatal exposure, it is essential to understand how monoclonal antibodies interact with the fetal body, especially given their nonlinear pharmacokinetics and long half-lives," they added. "A phase III randomized, controlled trial to assess treatment regimens is warranted; because nipocalimab will probably reduce the passive immunity of newborns, such a trial should follow surviving children."

The current phase II study enrolled 13 women at eight centers in seven countries. Intravenous nipocalimab (30 or 45 mg/kg of body weight per week) was administered from 14 to 35 weeks' gestation.

Intrauterine transfusions occurred less often and at a later gestational age in study pregnancies compared with recent qualifying pregnancies; 46% of study pregnancies received one or more intrauterine transfusions versus 85% of qualifying pregnancies, and median gestational age at first intrauterine transfusion was 27 weeks, 1 day for study pregnancies versus 20 weeks, 4 days for qualifying pregnancies.

Exchange transfusion was performed in one of 12 neonates from study pregnancies (who also received one simple transfusion) and in none of five neonates from qualifying pregnancies, they noted. Compared with four out of five infants from qualifying pregnancies, only six of 12 infants from study pregnancies had simple transfusions. All of the simple transfusions during the study occurred at more than 2 weeks of age.

Among the seven study pregnancies in which the primary endpoint was met, 46% of maternal-infant pairs received no antenatal or postnatal transfusions, and one neonate received one simple transfusion, they noted.

Limitations included the study's small sample size as well as the lack of blinding, randomization, placebo comparator, and representation of non-white patients, Moise and colleagues noted. Additionally, the historical cohort and qualifying pregnancies were managed outside of a study protocol, "possibly under different standards of care and with care obtained not at experienced referral centers."

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