Janssen Says Phase 2 Data in Small Study Demonstrate Potential Benefit of Therapy in HDFN

Rare Daily Staff

The Janssen Pharmaceutical Companies reported positive results from its phase 2, proof-of-concept, open-label trial for the treatment of pregnant individuals at high risk of early-onset severe hemolytic disease of the fetus and newborn.

The study showed a statistically significant (54 percent) proportion of 13 participants who received nipocalimab achieved the primary endpoint of a live birth at or after gestational age of 32 weeks without intrauterine transfusions. That compares to the historic reference point of 10 percent, which was derived from published and unpublished data. In the UNITY clinical trial, 12 of 13 participants experienced a live birth.

Among the seven participants who achieved the primary endpoint, the median gestational age at delivery was 37 and 1/7 weeks. The study, the company said, demonstrates the potential for nipocalimab to help address the underlying disease mechanism of high risk of early-onset severe (EOS) hemolytic disease of the fetus and newborn (HDFN). The results were presented at the Fetal Medicine Foundation World Congress in Valencia, Spain on June 26, 2023.

HDFN is a rare disease where maternal alloantibodies produced in a pregnant person’s immune system cross the placenta and attack fetal red blood cells—causing fetal red blood cell hemolysis, leading to anemia. The symptoms of HDFN can range from mild to life threatening. Some cases can involve neonatal jaundice or hyperbilirubinemia and severe cases can result in life-threatening fetal anemia requiring intervention to prevent development of fetal hydrops. With every pregnancy with an antigen-positive fetus, disease severity increases with an earlier gestational age of HDFN onset due to repeated alloimmunization. There are currently no approved non-surgical interventions for pregnancies at high risk of EOS HDFN in the United States. Pregnancies affected by severe HDFN may necessitate repeated IUTs, invasive and complex surgical procedures performed by specialists at specialized medical centers.

Nipocalimab was generally well tolerated across all the dose groups studied in pregnant individuals at high risk for EOS HDFN. One pregnancy resulted in fetal demise due to complications following an IUT performed at gestational age 22 and 5/7 weeks. These complications were considered unrelated to nipocalimab. There were no maternal or infant deaths. The most frequently reported adverse events were events that are not uncommonly reported in pregnancy or underlying HDFN.

Nipocalimab is an experimental, fully human, monoclonal antibody that is believed to selectively block the FcRn to reduce levels of circulating IgG antibodies, including autoantibodies and alloantibodies that underlie multiple conditions. Nipocalimab is the only anti-FcRn being studied across three key segments in the autoantibody space: maternal-fetal diseases mediated by maternal alloantibodies, rare autoantibody diseases, and prevalent rheumatological diseases. Blockade of FcRn by nipocalimab has the potential to reduce overall autoantibody levels while maintaining immune function. FcRn blockade is also believed to prevent placental transfer of maternal alloantibodies to the fetus.

The U.S. Food and Drug Administration granted Nipocalimab Fast Track designation in July 2019 and Orphan Drug designation in June 2020. The European Medicines Agency granted Nipocalimab Orphan Medicinal Product designation in October 2019 for the prevention of HDFN.

Janssen is planning a pivotal Phase 3 trial for nipocalimab in pregnancies at risk for severe HDFN.

“There is a significant unmet need to help address the serious and life-threatening health consequences of HDFN. Our aspiration is to transform the existing paradigm for families who endure the consequences of HDFN by seeking approval of a targeted and effective therapy,” said Katie Abouzahr, vice president of Autoantibody Portfolio and Maternal Fetal Disease Area Leader for Janssen Research and Development. “These phase 2 UNITY data in high-risk pregnancies demonstrated the important role that nipocalimab, an FcRn blocking antibody, may play in preventing the transfer of maternal alloantibodies through the placenta, thereby offering a potential treatment option for this devastating disease.”

Photo: Katie Abouzahr, vice president of Autoantibody Portfolio and Maternal Fetal Disease Area Leader for Janssen Research and Development