The Real-World Data of Emicizumab in Previously Untreated and Minimally Treated Patients with Hemophilia a Infants from China

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Introduction Emicizumab (EMI) is safe and efficient in pediatric patients with hemophilia A (HA). However, real-world data regarding immune response, pharmacokinetics (PK) and pharmacodynamics (PD) during EMI for previously untreated (PUP) and minimally treated (MTP) patients with HA infants(<3y) are limited in China. This study investigated the immune response and PK/PD of EMI in PUP and MTP with HA infants in China. Methods We performed a retrospective analysis of pediatric HA patients to collect data on PUPs and MTPs at our Comprehensive Hemophilia Care Center. Data included patients' baseline characteristics, therapy details, bleeding episode of pre- and post-EMI, and adverse events. Immune response included anti-emicizumab antibodies (ADAs) and factor VIII (FVIII) inhibitors. Laboratory analyses included FVIII-like activity and EMI concentration measurements. Results Sixteen PUPs and MTPs with HA had received EMI prophylaxis for a median (range) duration of 21.8 (4.9-47.0) months by July 2024. The median age at the beginning of EMI was 11.8 (5.8-33.3) months. At the initiation of EMI, all patients were inhibitor-negative. While on EMI, EMI showed effectively prevented bleeding even: the median annualized bleeding rate (ABR) of 0.6 (0.0-1.9), annualized joint bleeding rate (AJBR) of 0.0 (0.0-0.3), and annualized spontaneous bleeding rate (ASBR) of 0.0 (0.0-1.59). Seven(43.8%) patients reached zero-bleeding rate (ZBR). No drug-related serious adverse events were observed. In the loading phase, patients with median age of 10.8 (5.8-32.9) months and body mass index (BMI) of 17.8 (15.6-21.6) received a median EMI loading dose of 3.0 (2.4-3.5) mg/kg. Their median EMI concentration was 65.9 (36.2-79.9) μg/mL and FVIII-like activity was 27.0 (13.5-35.4) IU/dL. Even though the mdian EMI 4-weekly maintenance dosage [4.8 (4.0-5.6)mg/kg] was below the internationally recommended dosage (6mg/kg), patients reached EMI concentration of 50.2 (36.0-76.8) μg/mL, and FVIII-like activity of 14.9 (10.4-30.4) IU/dL. EMI concentration was correlated with FVIII-like activity (rs=0.858，p＜0.001). Four (25%) patients received a total of 9 administrations of factor-based therapy. During the long-term follow-up period, the median number of exposure days (EDs) was only 0 (0-3) days. No patients tested positive for ADAs or FVIII inhibitors. Conclusion EMI has demonstrated favorable tolerability and efficacy in PUPs and MTPs with HA in infants. Using EMI at substandard doses can still achieve relatively high maintenance concentrations. Furthermore, the concentration of EMI correlates well with their FVIII-like activity. No patients developed ADAs or FVIII inhibitors.