SUMMARY

• Nipocalimab, a fully human, effectorless anti-neonatal fragment crystallizable receptor (FcRn) monoclonal antibody, is an investigational agent 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
• 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.^1,3

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.^1,4,5
• 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.^1,4,5
• Approximately 80-85% of FNAIT cases in the Caucasian population are due to alloantibodies targeting the HPA-1a epitope.^1,4,6
• 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.⁵
• 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.^1,4,5

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

Study Design/Methods

• The study aims to enroll 50 pregnant patients who are at a risk for FNAIT.²
• 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 key inclusion and exclusion criteria, see Table Eligibility Criteria for Study Participation in the FREESIA-3 Study.

• The primary outcome is fetal/neonatal death or adjudicated severe bleeding up to the 1^st week post-birth or platelet count <30 × 10⁹/L.
• Select secondary endpoints include:
  • Platelet count at birth in neonates
  • Outcome of fetal/neonatal death reported up to 1^st week post-birth
  • Platelet count at birth in neonates, including <10, <30, <50, <150 x 10⁹/L
  • Nadir platelets count in neonates up to 1^st week post-birth
  • Neonates who require ≥1 platelet transfusion(s) up to 1^st week post-birth
  • Number of platelet transfusions per neonate reported up to 1^st week post birth
  • Number of donor exposures for a neonate who received ≥1 platelet transfusion(s) up to 1^st week post-birth
  • Adjudicated bleeding up to the 1^st week post-birth in fetus/neonate
  • Neonates who require IVIG for the treatment of thrombocytopenia up to 1^st week post-birth
  • Neonate/infant with treatment-emergent adverse events from day of birth to week 104

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.¹
• 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 <30x10⁹/L at birth.
• For study design/methods, see Figure: FREESIA-1 Study Design.

Literature Search

A literature search of MEDLINE^®, EMBASE^®, BIOSIS Previews^®, and DERWENT^® (and/or other resources, including internal/external databases) was conducted on 06 August 2024.