Key highlights in this article:
- Nipocalimab's Role in HDFN: Nipocalimab, an investigational drug, effectively reduces the risk of hemolytic disease of the fetus and newborn (HDFN) by blocking maternal antibodies from reaching the fetus.
- Significant Survival Improvement: In the phase 2 UNITY trial, 12 out of 13 babies survived, a significant improvement over the typical 38% survival rate in similar high-risk pregnancies.
- Safety and Future Research: The drug showed a favorable safety profile, with no increased risk of severe infections, leading to the initiation of phase 3 trials for broader maternal-fetal conditions like FNAIT.
Nipocalimab, a new investigational drug, has shown to mitigate the effects of hemolytic disease of the fetus and newborn (HDFN, according to findings from the phase 2 UNITY clinical trial published in the New England Journal of Medicine.1
Background
HDFN is a rare but severe condition that occurs when a pregnant woman’s immune system produces immunoglobulin G (IgG) antibodies that mistakenly target the red blood cells of the fetus. This can lead to serious complications, including severe anemia, jaundice, and, in severe cases, brain damage or death of the fetus or newborn.1
HDFN is caused by the transfer of harmful IgG antibodies from the mother's bloodstream to the fetus through the placenta. This transfer is facilitated by a specific receptor known as the neonatal fragment crystallizable receptor (FcRn). By blocking these receptors, nipocalimab aims to prevent the maternal antibodies from reaching the fetus and reducing the risk of HDFN. Additionally, the drug has been shown to lower IgG levels in the mother’s bloodstream, further decreasing the likelihood of fetal harm.1
The UNITY clinical trial, which is multinational in scope, involved a small cohort of pregnant women who were considered at high risk for HDFN due to their medical histories. Eleonor Tiblad, MD, PhD a physician and researcher at the Department of Medicine, Solna, Karolinska Institutet, led the Swedish portion of the study. Tiblad emphasized the significance of this development, particularly given the limitations of current treatments.1
“…Until now, the treatment of severe HDFN has consisted of repeated intrauterine blood transfusions (IUTs) to the fetus during pregnancy–an invasive and risky procedure that can lead to fetal death,” said Tiblad. “Neonatal intensive care, exchange transfusion, and repeated blood transfusions are often required after birth, so it is very valuable to have a drug that can prevent this.”1
Methods
The trial included 13 pregnant women from 8 medical centers around the world, who had experienced severe HDFN in previous pregnancies. These patients received nipocalimab between the 14th and 35th weeks of pregnancy. The outcomes were closely monitored, and children were monitored until the age of 2.2
Results
In the 13 participants treated with nipocalimab, nearly half (46%) of the babies did not require blood transfusions during either the fetal or neonatal periods. For those fetuses that did need transfusions during pregnancy, the onset of anemia was delayed by several weeks, allowing IUTs to be performed with significantly lower risk. Importantly, 54% of the fetuses passed the 32nd week of pregnancy without needing an intrauterine blood transfusion.2
One fetus did not survive due to complications from an IUT, but the overall survival rate was a notable improvement, with 12 out of 13 babies surviving. Tiblad emphasized the significance of this outcome, noting that “the survival rate is only around 38 percent in comparable pregnancies.”2
The trial's findings also highlighted the safety of nipocalimab, which was not associated with an increased risk of severe infections or immunological complications.2
The success of the phase 2 UNITY study has paved the way for a larger, randomized, placebo-controlled phase 3 trial, which is currently being conducted by Johnson & Johnson. The pharmaceutical giant is also exploring the use of nipocalimab in treating another IgG-mediated maternal-fetal disease, fetal neonatal alloimmune thrombocytopenia (FNAIT).2
References:
1. Karolinska Institutet. New investigational treatment may prevent severe disease in fetuses and newborns. Eureka Alert. August 7, 2024. Accessed August 21, 2024. https://www.eurekalert.org/news-releases/1053974
2. Moise KJ Jr, Ling LE, Oepkes D, et al. Nipocalimab in Early-Onset Severe Hemolytic Disease of the Fetus and Newborn. N Engl J Med. 2024;391(6):526-537. doi:10.1056/NEJMoa2314466
