Birmingham launches pioneering trial to improve pregnancy outcomes for severe haemolytic disease

A pioneering study that took place at Birmingham Women’s Hospital has found an antibody that can 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).

Pregnant mothers have taken part in the UNITY trial, which has found that nipocalimab, an investigational, fully human, monoclonal antibody, has the potential to improve the survival rate of these babies.

BHP members the University of Birmingham (UoB) and Birmingham Women’s and Children’s NHS Foundation Trust (BWC) 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.

Site investigator Mark Kilby, Emeritus Professor of Fetal Medicine at UoB and Honorary Consultant of Fetal Medicine at BWC 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.”

Haemolytic disease of the fetus newborn (HDFN), which is also sometimes referred to as Rhesus disease, is caused by a system of red blood cell antigens (most commonly of Rhesus D type) which raises the pathological antibody response in a pregnant person. These ‘pathological antibodies’ or alloantibodies can cross the placenta to the fetus and destroy its red cells, leading to progressive fetal anaemia and – if untreated – death of the fetus. 

Professor Kilby added: “These are fantastic results. In this group of pregnant women with severe HDFN, the medical management with nipocalimab has significantly reduced the need for early-onset in-utero fetal transfusion and improved the survival of these babies, reducing risks of miscarriage and stillbirth. Furthermore, and very importantly, nipocalimab seems to be well tolerated and safe for the mother and her unborn/newborn baby.   

“This research is a huge step forward for mothers who experience severe HDFN, as well as their partners, extended families, and of course, their children.”

Rosemary and Darren from Ireland were expecting baby Nessa when they took part in the clinical trial. Rosemary had had a previous in-utero transfusion for HDFN, and the couple had a child following treatment. Sadly, the couple lost a second baby after another in-utero transfusion. 

She was desperate to avoid another in-utero transfusion and was referred to the Fetal Medicine Centre at Birmingham Women’s Hospital eight weeks into her pregnancy after seeing news of the trial online and contacting her doctors at Dublin’s Rotunda Hospital. She had cell-free fetal DNA testing to confirm the baby was ‘suspectable’ to the antibodies she had produced. Rosemary then had maternal infusions of nipocalimab intravenously at weekly intervals from 14 to 35 weeks. 

Baby Nessa was born at 36 weeks weighing six pounds and 13 ounces and without the need for any IUTs.

Rosemary said: “When we were accepted onto the trial, we were both relieved and excited. Following the loss of our little girl Liliana, we were advised not to have any further pregnancies and we were devastated. This trial gave us hope of having another baby.”

“We were pregnant during the COVID lockdowns and as I was commuting from Ireland to Birmingham, it was a big worry but throughout our involvement in the trial, we felt supported, informed, understood and safe. We are forever grateful, the level of professionalism, compassion and empathy shown towards us is something we will never forget.” 

“Our two sons, Ollie and Joey now have a little sister, Nessa, who is a bubbly happy healthy four-year-old, full of mischief, giggles, and fun. To think the trial has given us what we believed was impossible, is a dream come true. To hear the trial has also given others living healthy children is fantastic. In a situation where we, like so many others felt was hopeless, to now know there is a treatment is like a miracle.”