Treatment with nipocalimab has shown positive results in delaying and preventing fetal anemia or intrauterine transfusions (IUTs) in individuals at risk for early-onset severe hemolytic disease of the fetus and newborn (HDFN), according to findings from the international phase 2 UNITY study recently published in The New England Journal of Medicine.
The anti-neonatal Fc receptor blocking antibody nipocalimab is known to inhibit transplacental transfer of immunoglobulin G (IgG) and to lower maternal IgG levels. Among patients with early-onset severe HDFN, the transplacental transfer of maternal antierythrocyte IgG alloantibodies is associated with fetal anemia, which, in turn, leads to the use of high-risk IUTs in an effort to prevent fetal hydrops and fetal death.
Early-onset HDFN, which is defined as “severe HDFN occurring at 24 weeks’ gestation or earlier,” is linked to considerable fetal and neonatal morbidity and mortality. Although the use of routine anti-Rhesus (Rh)D prophylaxis has led to significant reductions in RhD alloimmunization, early-onset severe HDFN nonetheless persists because of missed opportunities for administration and the lack of prophylaxis for non-RhD antigens.
In such high-risk pregnancies, the standard of care involves monitoring for fetal anemia via fetal blood samples and middle cerebral artery Doppler ultrasonography, followed by the use of well-timed IUTs. Complications associated with IUTs can occur, however, such as fetal death, premature rupture of the membranes, and preterm birth. The utilization of early IUT at <20 weeks’ gestational age (GA) is associated with a high rate of perinatal loss (ie, 17% per procedure).
Read more about the prognosis of HDFN
In the current study, the researchers sought to evaluate treatment with 30 or 45 mg of intravenous nipocalimab per kg per week, which was administered between 14 and 35 weeks’ GA among individuals at high risk for recurrent, early-onset severe HDFN. The primary efficacy endpoint was live birth at ≥32 weeks’ GA without the need for IUT. Secondary efficacy endpoints included the following:
- GA at time of the initial IUT
- Live birth at ≤24 weeks’ GA without the need for IUT
- Number of IUTs administered
- GA at delivery
- Fetal hydrops
- Receipt of phototherapy, an exchange transfusion (ET), or a simple erythrocyte transfusion in the first 12 weeks of life among neonates and infants
Between April 23, 2019, and Nov. 1, 2022, a total of 19 national or regional HDFN referral centers screened 23 patients with singleton pregnancies. Among these individuals, 13 women from were enrolled in the study.
Results of the study revealed that live birth at ≥32 weeks’ GA without the use of IUTs was reported in 54% (7 of 13) of the pregnancies (95% CI, 25%-81%; P <.001). No instances of fetal hydrops were reported. Overall, 46% (6 of 13) of the participants did not undergo an antenatal or neonatal transfusion.
Six of the fetuses received an IUT—five at ≥24 weeks’ GA and one prior to fetal death at 22 weeks’, five days’ GA. A live birth was reported in 12 pregnancies.
The mean GA at delivery was 36 week, 4 days. Among the 12 live-born neonates, one newborn received one ET and one simple transfusion, whereas five received simple transfusions only. Treatment-associated reductions in alloantibody titers and IgG levels were seen in cord blood and maternal samples.
“Nipocalimab delayed or prevented fetal anemia or [IUTs], as compared with the historical benchmark, in pregnancies at high risk for early-onset severe HDFN,” the authors noted. “These preliminary efficacy results, together with the preliminary safety data and evidence of the anticipated drug mechanisms, support the further evaluation of nipocalimab in severe HDFN.”
