FDA Grants Breakthrough Therapy Designation to Nipocalimab for the Treatment of Rare Disease in Pregnancy


In a study, nipocalimab helped more than 50% of patients with high-risk of hemolytic disease of the fetus and newborn achieve a safe live birth.

The FDA granted Breakthrough Therapy Designation (BTD) to nipocalimab for the treatment of alloimmunized pregnant individuals with high risk of early-onset severe (EOS) hemolytic disease of the fetus and newborn (HDFN)—a disease caused by maternal blood type being incompatible with fetal blood type—after reviewing positive data from the UNITY clinical trial, according to a recent Johnson & Johnson press release. This is the only therapy being developed to treat this rare condition.

HDFN is a condition that occurs during pregnancy when alloantibodies produced by the maternal immune system cross the placenta surrounding the fetus—these alloantibodies will attack the fetal red blood cells and cause conditions including fetal anemia and/or neonatal hyperbilirubinemia and anemia (life-threatening in the most severe cases.)

fetus inside the womb

Image credit: adimas | stock.adobe.com

"Nipocalimab represents a novel approach for the treatment of patients at risk of severe HDFN who need proven, safe, non-surgical solutions to help address the serious health consequences of this condition," said Katie Abouzahr, MD, vice president, Autoantibody and Maternal Fetal Immunology Disease area leader, Johnson & Johnson, in the press release.

Alloimmunized women produce an immune response when they are exposed to genetically different cells or tissues; in this case, this immune response can cause adverse events in the fetus. During UNITY (NCT03842189), a phase 2 global, multicenter, and non-blinded trial, investigators evaluated once-weekly intravenous infusion of nipocalimab for alloimmunized pregnant individuals (RhD or Kell) with a high risk of EOS HDFN.

Risk factors for EOS HDFN include obstetric history of severe fetal anemia, fetal hydrops, or previous stillbirth when gestation was at 24 weeks or less.

Investigators assessed efficacy, pharmacokinetics, and pharmacodynamics of nipocalimab in 13 participants, setting the primary end point as live birth at (or after) gestational age of 32 weeks without a need for an intrauterine transfusion (IUT) throughout the entire pregnancy. They also monitored maternal safety for 24 weeks post-delivery and infant safety for 96 weeks post-birth.

Once-weekly intravenous nipocalimab was shown to help most alloimmunized women (54%) achieve a safe live birth (at or after the gestational age of 32 weeks) without the need for IUT throughout the entire pregnancy. Because of to these positive efficacy and safety outcomes, it will be evaluated in the AZALEA phase 3 pivotal trial.

Nipocalimab is an investigational, high-affinity, fully human, aglycosylated, effectorless, monoclonal antibody that acts as an anti-neonatal Fc receptor (FcRn). Nipocalimab works by decreasing levels of alloantibodies and other circulating immunoglobulin G (IgG) antibodies in the mother without impacting immune function. FcRn inhibition is believed to prevent alloantibodies from entering the fetus, which can reduce the risk of HDFN.

In 2019, nipolcalimab received Fast Track designation in the United States and orphan medicinal product designation by the European Medicines Agency for the treatment of HDFN. In 2020, the FDA also granted it Orphan Drug status.

"We are committed to addressing the substantial unmet need in this devastating disease,” Abouzahr said.


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 REelase. February 9, 2024. Accessed on February 9, 2024. https://www.janssen.com/johnson-johnson-highlights-innovation-hemolytic-disease-fetus-and-newborn-hdfn-society-maternal

Recent Videos
Image Credit: © Anastasiia - stock.adobe.com
Image Credit: © Анастасія Стягайло - stock.adobe.com
hematological cancer/Image Credit: © nikola-master - stock.adobe.com
breast cancer treatment/Image Credit: © Siam - stock.adobe.com
small cell lung cancer treatment/Image Credit: © CraftyImago - stock.adobe.com
lymphoma, OPC, ASCO 2024, hodgkin lymphoma
Mid-section portrait of unrecognizable woman during last months of pregnancy holding her big belly gently standing against wall in blue room - Image credit: pressmaster | stock.adobe.com
palliative and hospice care/ Image Credits: © David Pereiras - stock.adobe.com