Johnson & Johnson’s nipocalimab, an investigational therapy currently being studied in clinical trials, shows promise in managing hemolytic disease of the fetus and newborn (HDFN), according to a review published recently in Vox Sanguinis.
Intravenous immunoglobulin (IVIG) has long been the most used method to delay or reduce the need for fetal blood transfusions, known as intrauterine transfusions (IUTs). However, it does carry additional risks and isn’t always effective, and as it is used off-label for HDFN, it is not widely adopted in clinical practice.
Nipocalimab, currently in clinical trials, offers a novel approach. It blocks the Fc receptor that helps maternal antibodies cross the placenta. By interfering with this pathway, nipocalimab may prevent harmful antibodies from reaching the fetus altogether. Its high binding strength—over 1,000 times greater than IVIg—makes it a compelling candidate for managing severe, early-onset HDFN.
IUTs have long been the standard treatment for HDFN, with a 97% fetal survival rate when performed in experienced centers. However, the procedure is technically demanding and riskier before 24 weeks of pregnancy. Complications such as miscarriage, premature birth and fetal death are more common when transfusions are needed earlier during pregnancy.
“The best therapy is prevention. The use of prenatal and immediate postnatal anti-D prophylaxis has substantially reduced cases of HDFN,” the authors wrote. “However, only D-induced disease is prevented, and not perfectly, and no such immunoprophylaxis exists for Kell, c or rarer antigen-induced HDFN.”
Read more about HDFN treatment and care
Weekly IVIg has shown moderate effectiveness in delaying the first IUT by about 15 days. This extra time can be critical, pushing the procedure to a later and safer point in pregnancy. A meta-analysis of 97 IVIg-treated pregnancies found that IVIG reduced the risk of fetal hydrops and fetal death while increasing overall survival at birth. However, IVIg is expensive and not without risks, including allergic reactions and potential infections.
“Additional prospective data will be collected on the pharmacokinetics, pharmacodynamics and objective effects of nipocalimab on the immune function of infants,” explained the authors.
These treatments are particularly important for women sensitized to red blood cell antigens such as Rhesus D, Kell, or ‘c’. Despite existing anti-D prophylaxis, about one in 1,000 pregnancies still develop alloimmunization, and no preventative treatment exists for non-D antigens. While screening and ultrasound monitoring help detect fetal anemia early, the availability of medical treatments may shift care away from invasive procedures.
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