Nipocalimab Shows Significant Promise Treating Early-Onset Severe Hemolytic Disease of the Fetus and Newborn
Results show nipocalimab could address the high unmet need of patients with severe hemolytic disease of the fetus and newborn, which is a life-threatening and rare condition with no other therapies currently in clinical development.
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Results from the Phase II UNITY trial demonstrated that nipocalimab delayed or stopped the development of severe fetal anemia requiring prenatal treatment and lowered the need for intrauterine transfusion (IUT) in pregnancies at high risk for recurrent early onset severe (EOS) hemolytic disease of the fetus and newborn (HDFN).1-3 Nipocalimab achieved the primary endpoint of the trial, with 54% of patients administered the drug having a live birth at or following 32 weeks gestational age (GA) without needing IUT, according to the study findings, published in The New England Journal of Medicine (NEJM).1
“The Phase II data published in the NEJM are encouraging, as the results support the potential of nipocalimab in the treatment of pregnant individuals with a history of severe HDFN, helping to establish a path forward for further development in this disease in a larger scale Phase III study,” UNITY lead investigator Kenneth J. Moise Jr, MD, professor, Department of Women’s Health and co-director, Comprehensive Fetal Care Center at Dell Medical School of the University of Texas at Austin, said in a press release. “For many patients, severe HDFN has a poor prognosis, and the current standard of care carries with it a high treatment burden, such as repeated IUTs and additional in-utero procedures that require access to specialty care and carry a risk to the life of the fetus. If approved, nipocalimab would be the first non-surgical treatment for pregnancies at high risk of HDFN.”3
HDFN occurs in pregnant individuals when alloantibodies generated by the maternal immune system cross the placenta surrounding the fetus. The alloantibodies then attack fetal red blood cells, causing conditions such as fetal anemia and/or neonatal hyperbilirubinemia and anemia, which can be life-threatening in the most severe cases. In February 2024, the FDA granted nipocalimab with Breakthrough Therapy Designation for this indication.4
Nipocalimab is a high-affinity, fully human, aglycosylated, effectorless, monoclonal antibody and acts as an anti-neonatal Fc receptor (FcRn). The drug reduces levels of alloantibodies and other circulating immunoglobulin G (IgG) antibodies in the mother without affecting immune function. Investigators hypothesize that inhibiting FcRn stops alloantibodies from entering the fetus, thereby lowering the risk of HDFN.
“Nipocalimab, a neonatal Fc receptor (FcRn) blocker, is under development for the treatment of multiple IgG autoantibody- or alloantibody-driven diseases,” the study authors wrote. “FcRn is the sole placental IgG transporter and salvage receptor that maintains circulating maternal serum IgG concentrations. FcRn blockade aims to inhibit alloantibody transfer to the fetus and to lower maternal IgG alloantibody titers.”1
The international, open-label, single-group UNITY trial analyzed treatment with intravenous nipocalimab at a dose of 30 mg or 45 mg per kilogram of body weight per week. The drug was administered from 14 to 35 weeks of gestation in patients with pregnancies at high risk for recurrent EOS HDFN.
Researchers screened 23 women with singleton pregnancies from April 23, 2019, to November 1, 2022, at national or regional HDFN referral centers. A total of 13 patients were enrolled in the study, with 14 pregnancies, at eight centers in seven countries. Investigators enrolled one participant twice, as the first pregnancy was excluded from the efficacy analysis because of early elective termination due to hyperoxaluria type I. The trial’s primary endpoint was live birth at 32 weeks of gestation or later without IUT as assessed against a historical benchmark.
The results show that live birth at 32 weeks of gestation or later without IUT occurred in seven of the 13 pregnancies (54%; 95% confidence interval, 25 to 81). There were no cases of fetal hydrops observed, with six patients who did not require antenatal or neonatal transfusions. Six fetuses required IUT, with five occurring at 24 weeks of gestation or later and one before fetal loss at 22 weeks and five days of gestation.
Live birth occurred in 12 pregnancies, with a median gestational age at delivery of 36 weeks and four days. Among the 12 live-born infants, one required an exchange transfusion and a simple transfusion, and five required a simple transfusion only. Investigators observed treatment-related reductions in the alloantibody titer and IgG level in maternal samples and cord blood. They did not observe any unusual maternal or pediatric infections. In terms of safety, serious adverse events were consistent with HDFN, pregnancy, or prematurity.
“We are committed to developing non-surgical options that are effective and have a proven safety profile for the treatment of alloantibody-driven maternal-fetal diseases,” Katie Abouzahr, MD, vice president, Autoantibody Diseases and Maternal-Fetal Immunology Disease Area Leader, Johnson & Johnson Innovative Medicine, said in the release. “The data published in the NEJM underscore the potential of nipocalimab to address the high unmet medical need in severe HDFN, a serious, life-threatening and rare condition in which no other therapies in clinical development exist.”3
References
1. Moise, Jr. K., et al. Nipocalimab in Early-Onset Severe Hemolytic Disease of the Fetus and Newborn. N Engl J Med 2024;391:526-537. DOI: 10.1056/NEJMoa2314466. Vol. 391 No. 6.
2. A Study to Evaluate the Safety, Efficacy, Pharmacokinetics and Pharmacodynamics of M281 Administered to Pregnant Women at High Risk for Early Onset Severe Hemolytic Disease of the Fetus and Newborn (HDFN). ClinicalTrials.gov ID. July 17, 2024. https://clinicaltrials.gov/study/NCT03842189
3. Groundbreaking nipocalimab study of pregnant individuals at high risk for early onset severe hemolytic disease of the fetus and newborn published in The New England Journal of Medicine. News release. Janssen. August 7, 2024. Accessed August 8, 2024. https://www.janssen.com/groundbreaking-nipocalimab-study-pregnant-individuals-high-risk-early-onset-severe-hemolytic-disease
4. Johnson & Johnson highlights innovation in hemolytic disease of the fetus and newborn (HDFN) at the Society for Maternal-Fetal Medicine’s (SMFM) 2024 Pregnancy Meeting. Janssen. News release. February 9, 2024. Accessed on August 8, 2024. https://www.janssen.com/johnson-johnson-highlights-innovation-hemolytic-disease-fetus-and-newborn-hdfn-society-maternal
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