Neonatal fragment crystallizable receptor (FcRn) inhibitors could significantly decrease complications associated with fetal and neonatal alloimmune thrombocytopenia (FNAIT), though investigations are still ongoing, according to a recently published American Journal of Hematology review.
“Numerous clinical trials are investigating therapeutic FcRn inhibition for various immune-mediated neuromuscular and rheumatologic conditions; however, FcRn inhibition also represents a potential therapy for IgG-mediated hematologic conditions,” the authors wrote.
The authors performed an extensive review in several medical databases including PubMed, clinicaltrials.gov, and Google Scholar, in search for relevant studies regarding the safety and efficacy of FcRn inhibitors such as nipocalimab in a variety of hematological conditions including FNAIT, hemolytic disease of the fetus and newborn (HDFN) and immune thrombocytopenia (IT).
Learn more about FNAIT therapies
Current Research on Nipocalimbab for FNAIT
Nipocalimab was granted fast-track U.S Food and Drug Administration (FDA) approval for pregnancies complicated with FNAIT earlier this year. The approval for FNAIT came shortly after approval for the treatment of HDFN, both conditions in which maternal antibodies destroy fetal cells.
Currently, a phase 3 clinical trial (FREESIA-1) is in progress evaluating the safety and efficacy of nipocalimab in FNAIT. Phase 3 clinical trials include large numbers of patients (usually in the hundreds or thousands) and compare the effectiveness of a drug against standard treatment or placebo; they represent the most critical phase of regulatory approval.
The FREESIA-1 trial will compare the platelet count and fetal outcomes up to 1 week after birth in patients receiving nipocalimab and placebo. The study is meant to start in October 2024, and the estimated completion date is 2029.
Potential benefits of FcRn Therapy in FNAIT
The FcRn function is to transport antibodies through mucosal barriers such as the placenta. Theoretically, inhibiting this receptor will prevent the transport of the maternal antibodies that target platelet antigens and produce a detrimental immune response against them.
Current therapeutic alternatives for FNAIT include intravenous immunoglobulin administration (IVIG); this treatment has proven to successfully reduce fetal complications in FNAIT. However, it can produce adverse effects such as severe infection and anemia.
Nipocalimab is meant to produce similar benefits with fewer adverse effects. However, the safety data for ongoing clinical trials is still pending.
“Ultimately, FcRn inhibition has the potential to mitigate the adverse fetal outcomes associated with RBC and platelet alloimmunization, with efficacy and safety data pending the completion of ongoing trials,” the authors concluded.
