Abstract
Introduction: Activated prothrombin complex concentrate (FEIBA, Takeda) and recombinant factor VIIa (rFVIIa, Novoseven, NovoNordisk) remain the primary bypassing agents (BPA) available for bleeding management in patients with hemophilia and inhibitors. Eptacog beta [rFVIIa-B, Coagulation factor VIIa (recombinant)-jncw, Sevenfact, HEMA Biologics & LFB] is a recombinant human FVIIa approved by the FDA in 2020 for the treatment of acute bleeding events in adult and adolescent patients ≥12 years old with hemophilia A or B with inhibitors. rFVIIa-B demonstrated hemostatic efficacy of 86% in a phase 3, randomized cross-over study of 465 mild/moderate bleeding events in 27 patients with hemophilia A and B with inhibitors. The purpose of this study is to report real-world data on the hemostatic efficacy of rFVIIa-B for acute bleeding management in patients with hemophilia A and B with inhibitors.
Methods: This is a retrospective chart-review of individuals ≥12 years of age with severe hemophilia A (factor VIII <1%) or hemophilia B (factor IX <1%) with an active inhibitor from 3 U.S. hemophilia treatment centers who utilized rFVIIa-B for acute bleed management.
Results: Seven bleeds were treated among the 3 patients identified. Patient characteristics and bleeding events are summarized in Table 1. The 3 patients were 12, 13, and 31 years of age. Two patients had hemophilia A and 1 patient had hemophilia B. The 2 patients with hemophilia A were on emicizumab prophylaxis per standard dosing regimens for bleeding prevention. The individual patient with hemophilia B had a history of anaphylaxis at inhibitor development and received on-demand BPA for acute bleeding events. All 7 bleeds consisted of hemarthroses with the knee being the primary site in 57% of the bleeds. Five of the 7 bleeds (71%) received a severe bleeding dose of 210-225 microgram per kilogram (mcg/kg) for the initial rFVIIa-B dose followed by 70-75 mcg/kg for subsequent doses. Final dosing regimens were dependent on available vial sizes. rFVIIa-B resulted in complete resolution of all bleeds (100%) at a median of 4 doses (range 1-8 doses) and a median of 24 hours (range 3-48 hours). There were no failures in bleeding resolution following treatment. No adverse events with infusions were reported including infusion-related reactions, hypersensitivity reactions, thrombosis, or thrombotic microangiopathy.
Conclusions: Administration of rFVIIa-B in the real-world setting appears to demonstrate hemostatic efficacy in a cohort of pediatric and adult patients with hemophilia A and B with inhibitors and may serve as an alternative human rFVIIa therapy for the management of acute bleeds in this population. Further post-marketing studies are warranted to expand the indication to younger children (<12 years of age) and to continue to monitor drug efficacy and adverse events in a larger population of patients over time including individuals on non-factor therapies such as emicizumab.
Batsuli: Bio Product Laboratory: Honoraria; Kedrion: Honoraria. Tran: HEMA Biologics: Honoraria. Young: Apcintex, BioMarin, Genentech/Roche, Grifols, Novo Nordisk, Pfizer, Rani, Sanofi Genzyme, Spark, Takeda, and UniQure: Consultancy; Genentech/Roche, Grifols, and Takeda: Research Funding. Sidonio: Guardian Therapeutics: Consultancy; Octapharma: Consultancy, Research Funding; Catalyst: Consultancy; Pfizer: Consultancy; Takeda: Consultancy, Research Funding; Biomarin: Consultancy; Novo Nordisk: Consultancy; Bayer: Consultancy; Genentech: Consultancy, Research Funding.
