OC07.03: Nipocalimab pharmacodynamics in a phase 2 study in pregnancies at risk of early‐onset severe hemolytic disease of the fetus and newborn

To evaluate drug pharmacodynamics in an open-label phase 2 study evaluating nipocalimab, an anti-FcRn (neonatal Fc receptor) blocking antibody, for prevention of fetal anemia, intrauterine transfusions (IUTs), and poor outcomes in pregnancies at high risk of early-onset severe hemolytic disease of the fetus and newborn (EOS HDFN). The UNITY study (Clinical trials.gov #NCT03842189) enrolled 14 RhD or Kell (K) alloimmunised singleton pregnancies with a prior obstetric history of HDFN onset at ≤24 weeks of gestation. One pregnancy was not included in analysis due to an early elective abortion for an unrelated reason. Weekly nipocalimab (30 or 45 mg/kg) was administered from 14 to 35 weeks of gestation with delivery targeted for 37 weeks of gestation. Pharmacodynamic markers, serum total IgG, alloantibody titer, and FcRn occupancy were assessed every 2 weeks in mothers and in cord blood at delivery or at IUTs. Full FcRn occupancy, IgG lowering, and alloantibody decreases were observed within 2 weeks after the initiation of nipocalimab treatment. Decreases from baseline for IgG ranged from –80% to –85% and for alloantibody titers ranged from 4- to 32-fold. FcRn occupancy was rapidly lost within 2-3 weeks after the last dose followed by rises in IgG and alloantibody titers. IgG and alloantibody titers from IUT cordocentesis (fetal) and in cord blood at delivery (newborns) were lower than concurrent maternal levels during full FcRn occupancy but were similar several weeks after dose cessation and loss of occupancy. Nipocalimab demonstrates rapid and reversible FcRn occupancy, lowering of maternal IgG alloantibodies and evidence for decreased placental IgG alloantibody transfer. As a result, nipocalimab warrants further evaluation in a global phase 3 study in HDFN.