Real-World Experience of Switching to Prophylactic Efanesoctocog Alfa in Patients with Moderate and Severe Hemophilia a: An Analysis of the Adelphi Hemophilia Wave III Disease Specific Programme

Introduction

Hemophilia A is an inherited condition characterized by a deficiency of clotting factor VIII (FVIII). Efanesoctocog alfa is a first-in-class, once-weekly, high-sustained FVIII replacement therapy. In the XTEND-1 trial, efanesoctocog alfa provided superior bleeding prevention compared with pre-study FVIII prophylaxis treatment, and normal to near-normal FVIII activity for the majority of the week (>40 IU/dL) in patients with severe hemophilia A aged ≥12 years. Treatment outcomes of efanesoctocog alfa in a real-world setting are yet to be reported.

Aim

To use real-world survey data to characterize patients with hemophilia A who switched to prophylactic efanesoctocog alfa and their clinical outcomes.

Methods

This interim analysis of a retrospective, observational study utilized data from the real-world Hemophilia Wave III Disease Specific Programme^TM, a cross-sectional survey with retrospective data collection capturing linked physician and patient data. A physician-completed patient record form captured clinical and treatment data. Patients in the United States with moderate or severe hemophilia A who had switched from prophylaxis with FVIII replacement therapy or non-factor therapy (emicizumab) to receiving efanesoctocog alfa prophylactically for ≥170 days were included in this analysis. Study objectives were to characterize included patients and to describe their clinical outcomes. Since patients were treated with efanesoctocog alfa for less than 12 months, ABR was estimated using the formula (number of bleeds/days on treatment) x 365 days. Data were collected for this interim analysis from July 2023–June 2024. Descriptive data are reported.

Results

In this interim analysis, 10 physicians provided data for 29 patients receiving efanesoctocog alfa. The mean (standard deviation (SD)) age was 26.4 (8.3; range of 4–49) years, 55% (n=16) of the patients were of white ethnicity; all patients were without inhibitors at the time of survey, with 7% (n=2) previously having had inhibitors; the mean (SD) time since initiating efanesoctocog alfa was 8.8 (2.3) months.

Prior to switching to efanesoctocog alfa, most patients (75% (n=21)) were previously treated prophylactically with standard half-life (SHL) FVIII replacement therapy; 18% (n=5) with extended half-life (EHL) FVIII replacement therapy; 4% (n=1) with non-factor therapy (emicizumab); 4% (n=1) with ‘other’ and 4% (n=1) were not recorded. Physicians reported that the most common reasons for their patients to change from their previous treatment were ‘too many infusions/injections’ (57% (n=16)), ‘more efficacious products available’ (43% (n=12)), ‘not being effective in preventing ABR’ (11% (n=3)) and ‘patient felt uncomfortable with the dosing schedule’ (11% (n=3)). The most frequently reported reason for prescribing efanesoctocog alfa prophylactically was ‘effectiveness in preventing ABR’ (76% (n=22)). In the 12 months prior to switching to efanesoctocog alfa treatment, the mean ABR was 1.07 (SD: 2.67; 95% confidence interval (CI) 0.04; 2.16), with 70% (n=19) of patients experiencing no bleeds, 15% (n=4) one bleed, 4% (n=1) 2 bleeds, 4% (n=1) 3 bleeds, 0% (n=0) 4 bleeds and 7% (n=2) five or more bleeds.

Ninety-six percent of physicians reported that they were ‘completely satisfied’ with efanesoctocog alfa for their patients. On efanesoctocog alfa, patients had a mean (SD) dosing interval of 6.9 (0.4) days. The mean (SD) dose of efanesoctocog alfa was 49.3 (3.8) IU/kg. The estimated mean ABR was 0.21 (SD: 0.66; 95% CI -0.04; 0.46). Since the initiation of efanesoctocog alfa treatment 89% (n=25) of patients experienced no bleeds, 4% (n=1) one bleed and 7% (n=2) two bleeds.

Conclusion

Consistent with clinical trial data, this real-world survey supports the effectiveness of switching from factor (SHL or EHL) replacement therapy or emicizumab to efanesoctocog alfa resulting in low bleeding rates. Additionally, most patients do not experience a bleed in the time after switching to efanesoctocog alfa. The frequency and dose of efanesoctocog alfa in a real-world setting is aligned with the United States prescribing information. The limitations of this study were the small sample size and the limited duration of efanesoctocog alfa treatment.

These data indicate that in a real-world setting, efanesoctocog alfa provides an effective alternative to existing treatments for hemophilia A, with a once-weekly dosing schedule.