Novel Drug May Decrease Risk of Severe Anemia in the Fetus, Newborn

The proof-of-concept, phase 2, open-label UNITY clinical trial showed positive topline results for JNJ-80202135 (nipocalimab; Janssen Pharmaceutical Companies of Johnson & Johnson), an investigative treatment for patients who are pregnant and at high risk of severe hemolytic disease of the fetus and newborn (HDFN).

“These early results represent an important step towards delivering a potential medication for expectant mothers at high risk of severe HDFN, and we are encouraged by what this treatment could mean for families affected by this potentially devastating disease,” said Katie Abouzahr, MD, vice president, Autoantibody Portfolio Development Leader, Janssen Research & Development, LLC, in a recent press release.

Most patients who were pregnant and received JNJ-80202135 did not need intrauterine transfusion (IUT) any time during the pregnancy to achieve a live birth at, or after, the gestational age (GA) of 32 weeks, meeting the primary endpoint. The IUT is a complex, invasive surgical procedure that is associated with an increased risk, and rate, of premature birth or fetal mortality.

Each year, approximately 80 out of 100,000 pregnancies are affected by HDFN, according to the American Journal of Obstetrics and Gynecology. HDFN occurs when a pregnant person’s immune system produces antibodies that attack the fetus’s red blood cells, which creates fetal hemolysis that can cause fatal anemia in the fetus. It is considered an ultra-rare, life-threatening disease to the fetus with no approved therapeutic treatment on the market.

JNJ-80202135 was evaluated for safety and efficacy in the global, multicenter, open-label, non-blinded phase 2 UNITY trial. The trial enrolled 14 high-risk pregnant women who received a weekly intravenous (IV) solution of JNJ-80202135. The investigators evaluated adverse events (AEs) for up to 96 weeks post-birth in children and 24 weeks in post-delivery parents.

The investigational drug is a high affinity, fully-human, aglycosylated, effectorless, monoclonal antibody that can selectively block the Fc receptor (FcRn). In effect, it can safely reduce autoantibody levels in the parent, and prevent maternal autoantibodies from entering and possibly harming the fetus, according to a Janssen press release.

The FDA granted JNJ-80202135 Fast Track designation in July 2019 and orphan drug status in June 2020. The European Medicines Agency also granted the drug orphan medicinal product designation in October 2019 for HDFN.

Ongoing studies are examining JNJ-80202135 as a treatment for maternal fetal diseases mediated by maternal autoantibodies (alloantibodies), rare autoantibody diseases such as autoimmune hemolytic anemia, and prevalent rheumatologic diseases—all of which are autoantibody-driven diseases.

“We look forward to sharing the full phase 2 results of the UNITY trial at an upcoming scientific medical meeting while we continue to plan for a pivotal phase 3 trial,” Abouzahr said in the press release.

Reference

Janssen Reports Positive Topline Phase 2 Results for Nipocalimab in Pregnant Individuals at High Risk for Severe Hemolytic Disease of the Fetus and Newborn (HDFN). Janssen. February 6, 2023. Accessed February 7, 2023. janssen.com/janssen-reports-positive-topline-phase-2-results-nipocalimab-pregnant-individuals-high-risk-severe