PB1159 - The Atlanta Study: Emicizumab and simoctocog alfa in previously untreated/minimally treated patients and in patients with inhibitors

Background: FVIII remains the first choice to treat bleeding events in hemophilia A. It is important to keep patients free of FVIII inhibitors, either by reducing the risk of inhibitor development or by eradicating inhibitors should they develop. Concomitant use of simoctocog alfa, a human cell-line derived recombinant FVIII, with emicizumab may be an effective approach to provide effective bleed prevention while establishing FVIII tolerance.

Aims: Part A: To evaluate the immunogenicity of low-dose FVIII given concomitantly with emicizumab in patients with little to no previous exposure to FVIII. Part B: to assess the efficacy and safety of concomitant emicizumab prophylaxis with FVIII for immune tolerance induction (ITI) in patients with inhibitors.

Methods: The Atlanta Study (NCT04030052) is a two-part, prospective, investigator-initiated, US multi-center study in patients with hemophilia A (≤2% FVIII:C). Part A enrolls previously untreated patients (PUPs) or minimally treated patients (MTPs; ≤2 exposure days [EDs] to FVIII) < 3 years of age and with no inhibitors. Patients receive standard emicizumab prophylaxis and 25 ± 5 IU/kg simoctocog alfa prophylaxis every 7–14 days until 50 EDs or 3 years, whichever comes first. The primary endpoint is the cumulative incidence of FVIII inhibitors. Part B enrolls patients < 21 years of age with inhibitors (>0.6 BU/mL). Patients receive standard emicizumab prophylaxis and simoctocog alfa ITI (100 IU/kg, 3x/week). The primary endpoint is the rate of ITI success. Secondary endpoints include bleeding rates, safety, and treatments used for breakthrough bleeds.

Results: The study is recruiting patients, with eight active sites across the US. Target enrolment is 40 participants for Part A, and 20 participants for Part B.

Conclusion(s): Results from the Atlanta Study may offer guidance to healthcare professionals on how to provide PUPs, MTPs, and patients with inhibitors with effective prophylaxis while striving to establish FVIII tolerance.