Effectiveness of emicizumab under real-world conditions in patients of all ages with hemophilia A with and without FVIII inhibitors: Third interim analysis of the non-interventional study EMIIL

Introduction: Emicizumab is a monoclonal, humanized bispecific antibody bridging coagulation factors IXa and X and thereby replacing the coagulation function of activated factor VIII (FVIII) even in the presence of FVIII inhibitors. Emicizumab is approved for routine prophylaxis in adult and pediatric patients with hemophilia A (PwHA) with or without FVIII inhibitors. Subcutaneous administration of emicizumab has demonstrated a positive benefit/ risk profile in clinical trial settings. The non-interventional study (NIS) EMIIL was initiated to generate additional evidence for long-term effectiveness under real-world conditions.

Method: EMIIL (ISRCTN58752772) is an ongoing single-arm, two cohorts, prospective, multicenter NIS in Germany and Switzerland collecting safety and effectiveness data in PwHA newly treated with emicizumab. The primary endpoint is the annualized bleeding rate (ABR) of treated bleeds, estimated using a negative binomial regression model. Here we report results from the third interim analysis of cohort A (PwHA without inhibitors).

Results: At data cut-off (May 15, 2023), a total of 112 patients with severe hemophilia A without inhibitors aged 0-75 years were available for evaluation of cohort A ([Fig. 1]). After a median treatment duration of 629 days (range 21-1244), the model-based ABR was 0.64 (95% CI 0.49-0.85). Zero treated spontaneous, joint, and target joint bleeds were recorded in 78.6%, 70.5%, and 95.5% of patients, respectively. Recorded in 12-week time windows, the majority of patients experienced zero treated bleeds across the study period (range 83.0-100.0%). At data cut-off, 66 (58.9%) patients experienced 218 adverse events, none of them leading to treatment discontinuation ([Fig. 2]).

Fig. 1 Results.

Fig. 2 Results.

Conclusion: The results from the third interim analysis on the effectiveness of emicizumab in a real-world setting, particularly data on ABR and the proportion of patients with zero bleeds, appear to be consistent with results from previous clinical trials. The same applies to the safety results from this third interim analysis as none of the patients developed new FVIII inhibitors and no new safety signals were identified with emicizumab.

Publikationsverlauf

Artikel online veröffentlicht:
13. Februar 2025