Oral Presentation Society of Obstetric Medicine of Australia and New Zealand ASM 2023

Safety and efficacy of nipocalimab in pregnant individuals at high risk for early-onset severe hemolytic disease of the fetus and newborn: results from the phase 2 UNITY study (#4)

Yosuke Komatsu 1 , Kenneth J Moise Jnr 2 3 , Leona Ling 1 , Dick Oepkes 4 , Enrico Lopriore 5 , Eleanor Tiblad 6 7 , Joanne EJT Verweij 4 , John Smoleniec 8 , Mark D Kilby 9 10 11 , Ulrich J Sachs 12 13 , Russell S Miller 14 15 , Roland Devlieger 16 , Jocelyn H Leu 1 , Arpana Mirza 1 , Valerie Smith 1 , Lisa B Schwartz 1 , May Lee Tjoa 1 , Shumyla Saeed-Khawaja 1 , James B Bussel 17
  1. Janssen R&D US, Janssen Pharmaceutical Companies of Johnson & Johnson, Horsham, Pennsylvania, United States
  2. Dell Medical School , University of Texas, Austin, Texas, United States
  3. Comprehensive Fetal Care Centre, Dell Children's Medical Centre, Austin, Texas, United States
  4. Department of Obstetrics, Department of Fetal Therapy, Leiden University Medical Centre, Leiden, The Netherlands
  5. Department of Pediatrics, University of Leiden Medical Centre, Leiden, The Netherlands
  6. Centre for Fetal Medicine, Karolinska University Hospital, Stockholm, Sweden
  7. Clinical Epidemiology Division, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden
  8. Feto-Maternal Unit, Liverpool Hospital, Liverpool, NSW, Australia
  9. University of Birmingham, Birmingham, United Kingdom
  10. Fetal Medicine Centre, Birmingham Women's and Children's Foundation Trust, Birmingham, United Kingdom
  11. Medical Genomics Research Group, Illumina, Birmingham, United Kingdom
  12. Institute for Clinical Immunology and Transfusion Medicine, Justus Liebig University, Giessen, Germany
  13. Department of Thrombosis and Haemostasis, Giessen University Hospital, Giessen, Germany
  14. Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Columbia University Irving Medical Center, New York, NY, United States
  15. New York-Presbyterian Hospital, New York, NY, United States
  16. Department of Obstetrics & Gynecology, University Hospitals KU Leuven, Leuven, Belgium
  17. Department of Pediatric Oncology/Haematology, New York Presbyterian Hospital/Weill Cornell Medical College, New York, United States

Introduction: The UNITY study evaluates the efficacy and safety of nipocalimab, a neonatal Fc receptor blocker, in reducing the risk of fetal anemia, intrauterine transfusions (IUT), and poor outcomes for pregnancies at high risk of early-onset severe hemolytic disease of the fetus and newborn (EOS-HDFN).

 

Methods: This open-label, single-arm study (NCT03842189) enrolled RhD or Kell alloimmunized pregnant individuals with singleton pregnancies at high risk for EOS-HDFN based on a prior obstetric history of fetal loss, fetal hydrops, severe fetal anemia, or need for IUT at ≤24 weeks gestational age (GA) due to HDFN. Weekly 30 or 45 mg/kg intravenous nipocalimab was administered between 14-35 weeks GA, with delivery targeted for 37 weeks GA. Follow-up was 24 weeks postpartum for mothers and 96 weeks postnatal for infants. The primary efficacy endpoint is the proportion of participants with a live birth at ≥32 weeks GA without an IUT. Secondary endpoints for antenatal and postnatal management are reported.

 

Results:  Of the total pregnancies (14), one pregnancy was not included due to early elective abortion for an unrelated reason. 54% (7/13) of participants achieved the primary efficacy endpoint of a live birth at >32 weeks GA without IUTs, with a median GA at delivery of 37 1/7 weeks (35 6/7–37 3/7). Twelve of 13 (92.3%) pregnancies resulted in a live birth with a median GA at delivery of 36 5/7 weeks (29 2/7–37 3/7). None of the 13 pregnancies developed fetal hydrops. One pregnancy resulted in fetal demise following complications of an IUT at 22 5/7 weeks GA. Of 12 live births, 11 (92%) neonates received phototherapy for median 87.0 hours (12–301). 50% (6/12) of neonates/infants received ≥1 simple transfusion in the first 12 weeks of life. The median number of simple transfusions was 2 (1–6), with 5 of 6 in pregnancies that received IUTs including 1 exchange transfusion. In 7 cases without an IUT, 1 infant had 1 simple transfusion. Four serious adverse events (SAEs) possibly related to nipocalimab occurred: fetal growth restriction, subchorionic hematoma, and fetal heart rate deceleration abnormality in one participant and placental abruption at delivery in another. One neonate delivered at 29 weeks developed a related SAE of neonatal respiratory distress. No maternal or neonatal/infant deaths occurred.

Conclusion: This study demonstrates the potential for nipocalimab to impact antenatal and postnatal management of fetal anemia in pregnancies at high risk for EOS-HDFN.