Pharmacodynamic Biomarkers in Infants with Hemophilia A Receiving Emicizumab in HAVEN 7

Background: Emicizumab, a bispecific antibody that mimics the cofactor function of activated factor (F)VIII, demonstrated a favorable safety and efficacy profile in infants with severe hemophilia A (HA) without FVIII inhibitors in HAVEN 7 (NCT04431726; Pipe et al. Blood 2022, 140[S1]: 457-459). It is known that some coagulation factors including FIX and FX, the binding targets of emicizumab, have lower plasma levels during the first 6 months of life. This research investigates whether the developing coagulation system impacts the pharmacodynamics (PD) of emicizumab prophylaxis in infants with HA enrolled to HAVEN 7 from birth to ≤ 12 months of age. Methods: Informed consent from the parents/legally authorized representative and ethics approval were obtained. PD was assessed by activated partial thromboplastin time (aPTT), FVIII activity using a chromogenic assay containing human FIX and FX (considered FVIII-like activity), and by FXIa-triggered thrombin generation (TG) assay. Plasma antigen levels of FIX and FX were determined using immunoassays. Plasma samples from 110 healthy infants (HIs; n=42, 0-3 months old; n=68, >3-24 months old) collected separately were also measured to generate age matched reference ranges. Results: In HAVEN 7, PD biomarkers, and FIX and FX plasma levels were assessed in 55 participants during the first 52 weeks of emicizumab exposure (data cut-off May 22, 2023). At baseline, mean FVIII activity was