Prospective Controlled Monitoring of Hemlibra Prophylaxis Initiation in a Large Cohort of Hemophilia a Patients- Real World Data

▪ Background: Hemlibra is a bispecific antibody that bridges factor IXa and factor X to restore hemostasis in patients with Hemophilia A (HA). It has proven efficacy and safety in multicenter trials. However, real world data is currently lacking. Ancillary tests' results for monitoring Hemlibra's hemostatic effect are scarce. Aim: To evaluate laboratory monitoring and any clinical correlations to hemostasis in patients with HA who initiate prophylactic treatment with Hemlibra, per standard protocol. Methods: Any severe HA patient with or without inhibitors treated by Hemlibra and followed by our National Hemophilia Center was eligible for the study, as approved by our institutional review board. The first two subcutaneous loading injections (3 mg/kg body weight given once weekly for 4 weeks) were administered in the clinic, as was the first post-loading maintenance dose (1.5 mg/kg given once weekly) injection. The patients were instructed to contact and consult the center about any trauma, bleeding or other adverse events. Bleeding episodes as well as any surgical intervention were documented. Blood samples were obtained before initiation of therapy, during the loading period (week 2), and following the initiation of maintenance therapy (week 5). Platelet-poor plasma (PPP) was obtained and activated partial thromboplastin time (aPTT), FVIII activity and inhibitor Bethesda units (BU) assay were performed. Hemlibra levels were evaluated as previously described.1 Thrombin generation (TG) was measured in PPP and thrombin peak height and endogenous thrombin potential (ETP) were calculated.2 Results: Forty patients with HA, median age 10 years (range 6 month- 76 years) were enrolled. The group consisted of 25 children and 15 adults, of whom 18 patients had FVIII inhibitors (median 16, range 1-900BU) and 22 were without inhibitors, including 9 patients with previous history of inhibitor. Patients were clinically followed for a median of 18 weeks (range 9-76 weeks). During follow-up only one patient experienced spontaneous bleeding episodes. Hemarthroses (mainly target joints) occurred in 4/40 patients (1 child only) and post traumatic bleeds were documented in 8 patients. However, 17/40 experienced trauma that did not cause any bleeding. For 32/40 patients, Hemlibra prophylaxis was sufficient to maintain hemostasis without additional supplemental therapy. Five minor surgeries were safely performed in 4 children (2/5 without supplemental therapy), yet another proc