Infant Immunity after Maternal Nipocalimab in Severe Hemolytic Disease of the Fetus and Newborn

BACKGROUND: Antenatal treatment with nipocalimab, a neonatal Fc receptor (FcRn) blocker, delayed or prevented fetal anemia, as compared with a historical benchmark, in a phase 2 study of early-onset severe hemolytic disease of the fetus and newborn (HDFN). We report on the fetal and neonatal pharmacokinetics of nipocalimab and infant immunity through 96 weeks after birth. METHODS: The UNITY study was a single-group, open-label study assessing pregnant individuals at high risk of early-onset severe HDFN treated with weekly intravenous nipocalimab (30 or 45 mg/kg) from 14 to 35 weeks' gestation, unless discontinued for safety-related stopping criteria or intrauterine transfusion initiation. Pharmacokinetics were assessed in maternal, fetal, and infant blood and colostrum or breast milk; FcRn receptor occupancy and immunoglobulin G (IgG) were measured in neonatal and maternal blood; and infant IgG and safety were monitored through 96 weeks after birth. RESULTS: Safety analysis included 12 live-born infants from 13 pregnancies (one fetal loss occurred following intrauterine transfusion complications). Nipocalimab concentrations were maintained in maternal participants at pharmacologically active concentrations (greater than 10 μg/ml) during the weekly dosing intervals, but were observed at low concentrations (10 μg/ml or less) in one of four fetal cordocenteses (0.04 μg/ml), one of 11 cord blood samples (0.7 μg/ml), three of seven colostrum samples (less than 4 μg/ml), and two of nine breast milk samples (less than 2 μg/ml). Low infant IgG at birth (cord blood median, 175 mg/dl; range, 92-941) reached levels consistent with a physiologic nadir by 24 weeks after birth (median, 273 mg/dl; range, 153-429) and recovered to normal range (with one exception) between 16 and 96 weeks (median, 762 mg/dl; range, 407-925). Infectious adverse events were primarily mild to moderate and typical for early childhood. Protective titers to age-appropriate vaccinations (diphtheria and tetanus) were observed in six of seven infants at or before 96 weeks. CONCLUSIONS: In this cohort of 12 live-born infants, antenatal treatment with nipocalimab resulted in low levels of detectable drug in fetal, neonatal, and infant samples. Treatment was associated with low IgG levels at birth; however, unusual or unexpected childhood illnesses or impaired vaccine responses were not observed. (Funded by Johnson & Johnson; ClinicalTrials.gov number, NCT03842189.).