The Benefit of FVIII Measurement: Tailored Treatment with Obi-1, a Recombinant Porcine Sequence Factor VIII, in Subjects with Acquired Hemophilia a

Introduction: A significant unmet need in the management of acquired hemophilia A (AHA) is a replacement therapy that can be used without consideration of anti-human FVIII titer and allows for the ability to measure FVIII levels. The ability to measure FVIII levels during treatment: (1) identifies treatment response and leads to the ability to individually tailor treatment; (2) reduces treatment safety concerns; and (3) optimizes the utilization of therapy during treatment to minimize cost impact. OBI-1 is a recombinant porcine sequence FVIII developed to meet this need.

Objective: To determine the impact of FVIII monitoring on OBI-1’s utilization during the treatment phase in the OBI-1 Phase 2/3 trial in AHA.

Methods: A post-hoc analysis of the utilization data from the prospective, open label, Phase 2/3 study of OBI-1 in AHA was conducted. Subjects were administered an initial dose of 200U/kg of OBI-1 and subsequent doses were based on subject’s post-infusion FVIII activity levels and clinical assessments. The impact of FVIII monitoring on OBI-1’s utilization was evaluated by comparing: (A) the initial administered dose to the subsequent doses infused in the treatment period; and (B) the initial total administered dose within the first 24 hours of treatment to the doses infused in the subsequent 24-hour period(s) in the treatment period. The magnitude and the statistical significance of the dose adjustment were determined using non-parametric statistics (signed rank test).

Results: Of the 29 subjects enrolled in the study, 65.5% (n=19) were males and median (range) age was 70 (42-90) years. Twenty-eight of the enrolled subjects had AHA while presence of anti-human FVIII titer could not be confirmed in the twenty-ninth subject. Of the subjects with AHA, 27 had a serious bleeding episode while one was enrolled for hemostatic cover for a planned surgery. Two subjects (7.1%) successfully responded requiring only the initial administered dose (100U/kg; 200U/kg). Two additional subjects were successfully treated within the first 24 hours. After the initial dose, subsequent doses indicated a median (IQR) dose reduction of 41.2% (50%) [n=26, p<0.01]. After the first 24-hour period, subsequent 24-hour periods showed a median (IQR) dose reduction of 65.4% (32.5%) [n=24, p<0.0001].

Conclusion: Study data indicate a significant reduction in the treatment dose after the initial dose or subsequent daily dosing after the first 24 hours. The ability to measure and monitor FVIII activity levels allow for the tailoring of OBI-1’s treatment dose and regimen. This measurability likely has a significant impact on dosing decisions to control the bleed.