EMIIL - Non-interventional study to investigate the effectiveness of Emicizumab under real-world conditions in pediatric, adolescent, adult and elderly patients with hemophilia A (PwHA) with and without FVIII inhibitors: an interim analysis

Introduction Emicizumab is a monoclonal, humanized bispecific antibody binding to coagulation factors IXa and X and thereby taking over the coagulation function of activated factor VIII (FVIII) even in the presence of FVIII inhibitors1. Emicizumab is approved for routine prophylaxis in adult and pediatric patients with hemophilia A (PwHA) with or without FVIII inhibitors. The safety and efficacy of Emicizumab has been described under clinical trial conditions and it has shown a positive benefit/risk profile in phase III trials (HAVEN 1-4)2–5. This prospective non-interventional study (NIS) EMIIL aims to better understand the long-term effectiveness of Emicizumab prophylaxis in PwHA with and without FVIII inhibitors under real-world conditions.

Method EMIIL (ISRCTN58752772) is a single-arm, two cohorts, prospective, multicenter, non-interventional study collecting primary observational data in hemophilia A patients newly treated with Emicizumab. According to the presence of FVIII inhibitors, patients are enrolled in one of the two cohorts ([Tab. 1]):

Tab. 1  Study Design.

- Cohort A: Patients with congenital severe hemophilia A without FVIII inhibitors- Cohort B: Patients with congenital hemophilia A with FVIII inhibitors

Results As of Oct 14th 2022, 106 PwHA have been enrolled. The initial results on the effectiveness of Emicizumab in a real-world setting, particularly the results on GLM model-based annualized bleeding rate (ABR) of treated bleeds and the proportion of patients with zero bleeds appear to be similar to the results of previous clinical trials (Table 1). The interim analysis reveals no new safety signals. Updated, detailed efficacy and safety assessments data will be shared at the GTH 2023 Congress, covering bleed- and safety-related endpoints.

Conclusion The result shown here is based on the first yearly interim analysis. Due to the small number of PwHA included in this interim analysis, no main conclusions can be drawn from the study data. The data reported at GTH 2023 will be based on the second interim analysis and will include updated effectiveness data for Emicizumab under real-world conditions in pediatric, adolescent, adult and elderly patients with hemophilia A (PwHA) with and without FVIII inhibitors from n = 86 study participants.[1] [2] [3] [4] [5] ([Fig. 1]).

Fig. 1 Demographics and Results of the first interim analysis.

Publication History

Article published online:
20 February 2023

• References

• 1 Kitazawa T, Igawa T, Sampei Z. et al. A bispecific antibody to factors IXa and X restores factor VIII hemostatic activity in a hemophilia A model. Nature medicine 2012; 18: 1570-4 https://pubmed.ncbi.nlm.nih.gov/23023498/
• 2 Pipe SW, Shima M, Lehle M. et al. Efficacy, safety, and pharmacokinetics of emicizumab prophylaxis given every 4 weeks in people with haemophilia A (HAVEN 4): a multicentre, open-label, non-randomised phase 3 study. The Lancet. Haematology 2019; 6: e295-e305 https://pubmed.ncbi.nlm.nih.gov/31003963/
• 3 Mahlangu J, Oldenburg J, Paz-Priel I. et al. Emicizumab Prophylaxis in Patients Who Have Hemophilia A without Inhibitors. N Engl J Med 2018; 379: 811-22 Lastname, GN, Lastname, GN YYYY, ‘Article’, Journal, Edition, Page, Place of publication: publishers
• 4 Young G, Liesner R, Chang T. et al. A multicenter, open-label phase 3 study of emicizumab prophylaxis in children with hemophilia A with inhibitors. Blood 2019; 134: 2127-38 https://pubmed.ncbi.nlm.nih.gov/31697801/
• 5 Oldenburg J, Mahlangu JN, Kim B. et al. Emicizumab Prophylaxis in Hemophilia A with Inhibitors. N Engl J Med 2017; 377: 809-18