Sicherheit und Wirksamkeit von Nipocalimab bei Schwangeren mit hohem Risiko für eine früh einsetzende schwere hämolytische Erkrankung des Feten und des Neugeborenen (HDFN): Ergebnisse der Phase-2-Studie UNITY
Kenneth J. Moise (Austin, TX / US), Leone E. Ling (New Jersey, CN / US), Dick Oepkes (Leiden / NL), Enrico Lopriore (Leiden / NL), Eleonor Tiblad (Stockholm / SE), Joanne Verweij (Leiden / NL), John Smoleniec (Liverpool / AU), Gregor Bein (Gießen / DE), Ulrich Sachs (Gießen / DE), Mark D. Kilby (Birmingham / GB), Russell S. Miller (New York, NY / US), Roland Devlieger (Leuven / BE), Jocelyn H. Leu (New Jersey, CN / US), Mirza Arpana (New Jersey, CN / US), Valerie Smith (New Jersey, CN / US), Lisa B. Schwartz (New Jersey, CN / US), May Lee Tjoa (New Jersey, CN / US), Shumyla Saeed-Khawaja (New Jersey, CN / US), Yoskue Komatsu (New Jersey, CN / US), James B. Bussel (New York, NY / US), the UNITY Study Group (Austin, TX / US)
The UNITY phase 2 study evaluates the efficacy and safety of nipocalimab, a neonatal Fc receptor (FcRn) blocking monoclonal antibody, to reduce 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). Nipocalimab aims to inhibit placental transfer of HDFN-associated alloantibodies from mother to fetus and to lower circulating maternal alloantibody levels.
This open-label, single-arm study (NCT03842189) enrolled RhD (D) or Kell (K) alloimmunized individuals (fetal anti-D ≥32 and anti-K ≥4, 8–14 weeks [wks] gestational age [GA] at screening) with singleton pregnancies at high risk for EOS-HDFN. Weekly 30 or 45 mg/kg intravenous nipocalimab was administered between 14-35 wks GA, with delivery targeted for 37 wks, and follow-ups at 24 wks postpartum (mothers) and 96 wks postnatal (infants). Primary efficacy endpoint is proportion of pregnancies with a live birth at ≥32 wks GA without an IUT. Secondary endpoints will report antenatal and postnatal management.
Of 14 pregnancies enrolled with high risk EOS-HDFN, 1 was not included and 12/13 (92.3%) pregnancies were live births (median GA at delivery =36 5/7 wks [29 2/7–37 3/7]), of which 7 were at >32 wks GA without IUTs (median GA=37 1/7 wks [35 6/7–37 3/7]) and 5 were with IUT (IUT initiation ≥28 wks). One pregnancy resulted in fetal demise (IUT complications). Of 12 live births, 11 received phototherapy (median 87.0 hours [12–301]) and 6 received ≥1 simple transfusion (median number 2 [1–6], in first 12 weeks of life; 5 IUTs, 1 exchange transfusion). No maternal/neonatal deaths/serious infections; 4 fetal SAEs occurred: fetal growth restriction, subchorionic hematoma, fetal heart rate deceleration, and placental abruption at delivery.
This first prospective interventional study demonstrates the potential for nipocalimab, an FcRn blocking antibody, to alter the underlying disease mechanism impacting the antenatal and postnatal management of fetal anemia in pregnancies at high risk for EOS-HDFN. These findings support a favorable benefit–risk profile of nipocalimab and warrant further evaluation of this drug in a phase 3 trial in pregnant individuals at risk for severe HDFN.
KJM serves as the overall principal investigator for the phase 2 trial of nipocalimab (UNITY); has received funding from Momenta Pharmaceuticals, Inc., paid on his behalf to the McGovern Medical School–UT Health and from Janssen Pharmaceuticals, Inc., paid on his behalf to Dell Medical School at The University of Texas at Austin for a clinical trial on a monoclonal antibody for the treatment of HDFN; has served on the steering committees and advisory boards for clinical studies for Momenta Pharmaceuticals, Inc., and Janssen Pharmaceuticals but has not received funding for these activities; receives royalty funding from UpToDate, Inc., for authorship on various chapters, consulting fees from Health Management Associates, Inc., for consultation on the formation of fetal centers, consulting fees from BillionToOne, Inc., paid on his behalf to Dell Medical School at The University of Texas at Austin, and honoraria from GLC Healthcare, Inc., for podcast content on HDFN; and serves as a nonpaid consultant for immunology for Janssen Pharmaceuticals, Inc.
LEL, JHL, AM, VS, LBS, MLT, SS-K, and YK are employees of Janssen Research & Development, LLC, and hold stock/stock options from Johnson & Johnson.
DO, EL, and ET have received consulting fees for membership of steering committees and advisory boards for clinical studies from Momenta Pharmaceuticals, Inc., and Janssen Pharmaceuticals, Inc.
EV serves as the principal investigator of UNITY and CLARITY studies in The Netherlands.
JS, UJS, RSM, and RD have no conflicts of interest.
MDK serves as the chair of the RCOG Genomic Taskforce and as a senior principal clinical scientist in the Medical Genomics Research Group, UK.
JBB has receivedconsulting fees for membership of advisory boards for Janssen Pharmaceuticals, Inc., UCB, Argenx, and Rallybio.