Johnson & Johnson's nipocalimab has shown promising results in a Phase 2 open-label UNITY study for treating alloimmunized pregnant individuals at high risk of early-onset severe hemolytic disease of the fetus and newborn (HDFN). The study, published in The New England Journal of Medicine, demonstrated a significant improvement in live birth rates without the need for intrauterine transfusions (IUT). This offers a potential non-surgical treatment option for a condition with limited interventions.
UNITY Study Results
The UNITY study met its primary endpoint, with 54% of individuals receiving nipocalimab achieving a live birth at or after 32 weeks gestational age (GA) without requiring IUT (95% CI, 25.1-80.8; P<0.001), compared to a historical benchmark of 10%. The study enrolled pregnant individuals at high risk for recurrent early-onset severe HDFN, assessing intravenous nipocalimab administration from 14-35 weeks. The results indicated that nipocalimab effectively delayed or prevented severe fetal anemia, reducing the need for IUTs.
"The Phase 2 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 3 study," said Kenneth J. Moise Jr., M.D., Professor at Dell Medical School of the University of Texas at Austin and lead study investigator.
Impact on Pregnancy Outcomes
Compared to qualifying pregnancies, the UNITY study pregnancies showed a higher proportion of live births (92% versus 38%), fewer participants requiring IUTs (46% versus 85%), a later median GA at first IUT (27 and 1/7 weeks versus 20 and 4/7 weeks), and a later median GA at delivery (36 4/7 weeks versus 23 and 6/7 weeks). Notably, none of the study pregnancies developed hydrops, whereas seven fetuses in the most recent qualifying pregnancies did.
Safety Profile
The most frequently reported adverse events in the UNITY study were consistent with those common in pregnancy and HDFN. Serious side effects were also consistent with HDFN or other pregnancy-related conditions, such as subchorionic hematoma and premature separation of the placenta. Infections and illnesses in infants of mothers exposed to nipocalimab were consistent with those typically observed in the neonatal and infancy period. No maternal or neonatal/infant deaths occurred during the study, though one pregnancy resulted in fetal demise related to a complication of an IUT.
Ongoing Research
The positive efficacy and safety results from the UNITY study support further clinical development of nipocalimab for treating severe HDFN. The AZALEA Phase 3 pivotal study is currently enrolling pregnant individuals at risk for severe HDFN with a history of the condition to further evaluate nipocalimab's efficacy and safety. Johnson & Johnson is also conducting a Phase 3 study of nipocalimab in fetal and neonatal alloimmune thrombocytopenia (FNAIT).
About HDFN
Hemolytic disease of the fetus and newborn (HDFN) is a rare condition arising from maternal-fetal incompatibility in red blood cell types. Maternal alloantibodies attack fetal red blood cells, causing fetal anemia. Severe HDFN can lead to life-threatening fetal anemia requiring repeated intrauterine transfusions (IUTs), which carry risks of fetal mortality and premature birth. It is estimated that up to 80 of every 100,000 pregnancies in the U.S. are affected by HDFN each year.
Nipocalimab: Mechanism of Action
Nipocalimab is an investigational monoclonal antibody designed to bind with high affinity to block FcRn and reduce levels of circulating immunoglobulin G (IgG) antibodies, including autoantibodies and alloantibodies, without causing broad immunosuppression. This blockade is believed to prevent the transplacental transfer of maternal alloantibodies to the fetus.
