166: Fetal & Neonatal Drug Exposure Following Nipocalimab Treatment in Pregnant Women at Risk of EOS-HDFN

Statement of Purpose, Innovation or Hypothesis: Nipocalimab is a fully human, anti-neonatal Fc receptor (FcRn) blocking antibody that is under evaluation for the treatment of early-onset severe hemolytic disease of the fetus and newborn (EOS-HDFN) based on its potential to block placental transfer of FcRn-mediated maternal to fetal IgG alloantibodies, with insignificant placental transfer of nipocalimab itself. To evaluate the placental transfer of nipocalimab in pregnancy, serum nipocalimab concentrations were evaluated in fetal and neonatal participants whose mothers received nipocalimab in the Ph2 UNITY study.

Description of Methods & Materials: UNITY is a Ph2, multicenter, open-label, single-arm study evaluating the safety, efficacy, PD, and PK of nipocalimab in 14 pregnancies at high risk of EOS-HDFN who were treated with 30 or 45 mg/kg weekly intravenous nipocalimab from 14 weeks and up to 35 weeks gestational age (GA) with planned deliveries at 37 weeks GA. To evaluate serum nipocalimab concentrations, one blood sample was collected from fetuses during a clinically indicated cordocentesis as well as from neonates in cord blood at birth and venous blood at Week 4 postpartum.

Data & Results: Of the 14 pregnancies, 13 were included in the PK analysis; 1 participant enrolled twice, and only latter was included. Of the 13 pregnancies, 12 resulted in live births, 1 resulted in fetal loss due to IUT, and 6 required cordocentesis. Nipocalimab was detected in 1/5 available fetal samples (0.04 μg/mL) and 1/11 available neonatal samples at birth (0.7 μg/mL) but was undetectable in all neonates at Week 4 postpartum. The detectable nipocalimab concentrations were observed in a single fetus and in a different single neonate during the study. Neonatal serum IgG was low at birth especially when maternal treatment ended approximately 2 weeks before delivery.

Interpretation, Conclusion or Significance: These observations imply minimal fetal and neonatal drug exposure upon maternal nipocalimab dosing and that low neonatal IgG may be the result of nipocalimab inhibition of placental IgG transfer. The potential for nipocalimab exposure in the fetus and newborn will be further evaluated in a Ph3 study.

Disclosures: EL, JHL, JZ, YX, LEL, KC, UA, WS, SSK, AM, YK, JW, KK, RRC, MS, AV are employees of Janssen/Johnson & Johnson Innovative Medicine and may hold stock/stock options from Johnson & Johnson.

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Additional Information/Authors: Umair Amin, MBBS, Waheeda Sirah, MS, Yosuke Komatsu, MD, PhD, FACOG, Jannine Williams, MBA, Kattayoun Kordy, MD, Ricardo Rojo Cella, MD