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.).