Investigational human, monoclonal antibody nipocalimab may improve survival of unborn babies with haemolytic disease of newborn: Study

Pregnant mothers have taken part in a clinical study (the UNITY trial) in Birmingham, which has found that nipocalimab, an investigational, fully human, monoclonal antibody, has the potential to improve the survival rate of unborn babies with rare, early-onset fetal anaemia, as a result of haemolytic disease of the fetus and newborn (EOS-HDFN).

The study investigated pregnancies complicated by severe EOS-HDFN (RhD (D) or Kell (K) alloimmunized pregnant individuals with singleton pregnancies) and evaluated the effects of nipocalimab at weekly intervals from 14-35 weeks of pregnancy.

The University of Birmingham and Birmingham Women’s Children’s NHS Foundation Trust were a study site for a global, multicentre, open-label trial, in which nipocalimab was given for the treatment of pregnancies at high risk of severe EOS-HDFN, and evaluated safety, efficacy, and the maternal metabolism of the monoclonal antibody.

Nipocalimab is an investigational monoclonal antibody, purposefully designed to bind with high affinity to block the fetal/neonatal fragment crystallizable (Fc) receptor (FcRn) and reduce levels of circulating immunoglobulin G (IgG) antibodies, including alloantibodies and autoantibodies that underlie multiple conditions. Blockade of IgG binding to FcRn in the placenta is also believed to prevent transplacental transfer of maternal alloantibodies to the fetus.

Results from a Phase 2 clinical trial published in the New England Journal of Medicine, sponsored by Johnson and Johnson, have demonstrated the majority of pregnant patients with severe HDFN who received nipocalimab achieved a live birth at or after the gestational age of 32 weeks, without the need for an intrauterine transfusion (IUT) throughout their entire pregnancy.

The study demonstrated that 54% of pregnant women treated with nipocalimab gave birth at or after 32 weeks of pregnancy, without any IUTs, compared to 0% in their previous pregnancy. Overall, the perinatal survival was 92%, whereas historically only 10% of pregnancies affected by severe HDFN reach this benchmark.

Of the 46% requiring IUT, the majority were after 24 weeks of pregnancy, and only a single case was performed at 22 weeks, which sadly was complicated by a miscarriage. Nipocalimab was well tolerated by pregnant individuals and newborn/infants with no unusual infections despite IgG lowering in pregnancy. Serious adverse events were generally consistent with pregnancy conditions, HDFN outcomes, and gestational age at birth.

The Birmingham site investigator, Mark Kilby, Emeritus Professor of Fetal Medicine at the University of Birmingham and Honorary Consultant of Fetal Medicine, Birmingham Women’s and Children’s NHS Foundation Trust said:

“For mothers with severe HDFN the outcome not only of the condition but of the treatment, can be devastating. This is why the search for therapies to reduce the consequences of the maternal immune response has been focused on this cohort of women. The clinical study has found that nipocalimab is well tolerated and greatly increases the chance of unborn babies surviving severe EOS-HDFN, requiring less in-utero transfusion therapy.”

The promising results of the UNITY study have prompted the U.S. Food and Drug Administration (FDA) to grant a Breakthrough Therapy Designation (BTD) for nipocalimab for the treatment of alloimmunized pregnant individuals with HDFN. The AZALEA Phase 3 pivotal trial is currently enrolling pregnant individuals who are at risk for severe HDFN at any gestational age, who have a history of severe HDFN in a prior pregnancy.