SUMMARY

• Nipocalimab is an investigational, fully human, high-affinity, aglycosylated, effectorless, immunoglobulin G1 (IgG1) anti-neonatal fragment crystallizable receptor (FcRn) monoclonal antibody that is being studied for the treatment of fetal and neonatal alloimmune thrombocytopenia (FNAIT) in at-risk pregnancies.¹
  • By interfering with the binding of immunoglobulin G (IgG) to FcRn with high affinity and selectivity, nipocalimab inhibits maternal placental IgG transfer and lowers circulating maternal IgG levels.
• An ongoing, phase 3, multicenter, randomized, open-label study (FREESIA-3; NCT06533098) is evaluating the efficacy and safety of nipocalimab in pregnant patients who are at risk for severe FNAIT.^2,3
• An ongoing, phase 3, multicenter, randomized, double-blind, placebo-controlled study (FREESIA-1; NCT06449651) is evaluating the efficacy and safety of nipocalimab in pregnant patients who are at risk for FNAIT.^1,4
• A global, retrospective chart review (FREESIA-2) is evaluating the treatment patterns, outcomes, and management of pregnant patients treated with nipocalimab who are at risk for FNAIT.⁵

BACKGROUND

• FNAIT is a rare, pregnancy-associated condition that occurs when there is incompatibility between the human platelet antigen (HPA) types of a pregnant women and the fetus.^1,6,7
• Maternal IgG alloantibodies, which can be formed due to exposure to incompatible, paternally-derived fetal HPA, cross the placenta during pregnancy by binding to FcRns, leading to the destruction of platelets and varying degrees of thrombocytopenia in the fetus and neonate.^1,6,7
• Approximately 80-85% of FNAIT cases in the Caucasian population are due to alloantibodies targeting the HPA-1a epitope.^1,6,8
• The effect of maternal anti-HPA-1a antibodies on the fetus is clinically highly heterogenous, as most fetuses remain asymptomatic while others can develop bleeding under the skin (petechiae) or internal organ bleeding.⁷
• The most severe symptom is intracranial hemorrhage (ICH) which can be seen in about 10-20% cases and can lead to neurological complications or death.^1,6,7

CLINICAL DATA

Phase 3 Study: FREESIA-3

An ongoing phase 3, multicenter, randomized, open-label study (FREESIA-3) is evaluating the efficacy and safety of nipocalimab in pregnant patients who are at risk for severe FNAIT.^2,3

Study Design/Methods

• The study aims to enroll approximately 50 pregnant patients who are at a risk for FNAIT.
• Patients with alloantibodies against HPA-1a and/or HPA-5b will be randomized to receive either:
  • Intravenous (IV) nipocalimab administered from gestational age (GA) of week 13-16 until before delivery
  • IV immunoglobulin (IVIG) starting from GA week 12 for high-risk pregnancies or GA week 20 for standard-risk pregnancies, in combination with oral prednisone as per study protocol
• For study design, see Figure: FREESIA-3 Study Design.

Phase 3 Study: FREESIA-1

An ongoing, phase 3, multicenter, randomized, double-blind, placebo-controlled study (FREESIA-1) is evaluating the efficacy and safety of nipocalimab in pregnant patients who are at standard risk for FNAIT.¹

Study Design/Methods

• The study aims to enroll approximately 39 anti-HPA-1a alloimmunized pregnant patients with an estimated GA of 13-16 weeks.
• The primary composite endpoint will assess the adverse outcome of fetal or neonatal death or adjudicated severe bleeding in uteruo or up to the first week post birth, or a neonatal platelet count of <30×10⁹/L at birth.
• For study design/methods, see Figure: FREESIA-1 Study Design.

Retrospective Chart Review

FREESIA-2

Zaha et al (2024)⁵ presented the study design of a multicenter, retrospective chart review (FREESIA-2) that aims to evaluate the treatment patterns, outcomes, and management of pregnant patients treated with nipocalimab who are at risk for FNAIT.

Study Design/Methods

• The study aims to collect historical data from medical records of pregnant patients at risk for FNAIT and of neonates born from such at-risk pregnancies (N~300).
• The study identification period for pregnancies at risk for FNAIT was from January 1, 2018, to December 31, 2023 (in all selected countries except Norway). In Norway, the identification period began from January 1, 1997.
• Key inclusion criteria:
  • Patients aged ≥18 years at the time of their first recorded pregnancy
  • History of ≥1 prior FNAIT-affected pregnancy
• Selected data analyses and outcomes:
  • Demographic data of pregnant patients
  • Adverse outcome of fetal or neonatal death or severe bleeding (ICH or non-ICH) or a neonatal platelet count at birth <30×10⁹/L
  • Proportion of neonates with a neonatal platelet count at birth <10×10⁹/L, <30×10⁹/L, <50×10⁹/L, <100×10⁹/L, or <150×10⁹/L
  • Neonatal platelet count nadir from birth to 1 week after delivery
  • Platelet count at birth
  • Proportion of neonates requiring platelet transfusion(s)
  • Number of neonatal platelet transfusions required
  • Proportion of neonates with minor bleeds (eg, petechiae, hematoma, and hematuria)
  • Proportion of neonates requiring IVIG
  • Number of neonatal IVIG infusions required
  • Proportion of preterm births (defined as GA <32 weeks)
  • Proportion of neonates with a birth weight below the 10th percentile of GA
  • Proportion of neonates affected by fetal growth restriction, as defined by fetal growth charts
  • Titers of anti-HPA antibodies in maternal blood over time during pregnancy and postpartum period
  • Serious adverse events, including hospitalizations, death, congenital abnormalities, and maternal outcomes (eg, preeclampsia)
• Statistical analyses:
  • Mean, median, standard deviation, and interquartile range for continuous endpoints
  • Proportion and 95% confidence interval for binary and categorical endpoints.
  • Analyses will be grouped by standard-risk vs high-risk pregnancies, pregnancies treated vs not treated with IVIG, and combinations of these subgroups and categorizations.
    • Endpoint analyses will also be presented by various subgroups, including (but not limited to) age of the pregnant patient, calendar years of the pregnancies, and geographic regions.

Literature Search

A literature search of MEDLINE^®, EMBASE^®, BIOSIS Previews^®, and DERWENT^® (and/or other resources, including internal/external databases) was conducted on 20 January 2025.