United States Post-Marketing Safety (PMS) Study of rpFVIII in Patients with Acquired Hemophilia A: Preliminary Data

Introduction: Acquired hemophilia A (AHA) is a rare autoimmune disorder characterized by development of neutralizing autoantibodies to circulating factor VIII (FVIII). Obizur^® is a recombinant, B-domain deleted, porcine-sequence FVIII (rpFVIII) with low cross-reactivity to anti-human-FVIII antibodies for the treatment of AHA. The objective of this study is to collect data assessing the safety, safety-related factors, utilization, and effectiveness of rpFVIII in real-world clinical practice.

Methods: This is a multi-center, non-controlled, open-label, non-interventional Post-Marketing Safety (PMS) surveillance study conducted in the United States for AHA patients treated with rpFVIII. This is a prospective and retrospective data will a target enrollment of 40 patients. Statistical analyses will be conducted and include, specifically but not exclusively, descriptive statistics.

Results: A second, preliminary, unplanned data read-out was conducted on March 31, 2017, on 19 patients (11 males and 8 females) from 11 centers in the US. Complete demographic data was available for 15 patients and they had a median age of 73 years (range: 54-81) and the median weight was 85.1 kg (range: 43.7-159.3). The mean lag time of AHA diagnosis was 13.2 days (range: 16 [pt with no bleed at the diagnosis] -127) and the median was 6 days. The mean days from bleeding onset to first Obizur infusion was 98.1 (range: 3-581) with a median of 19 days. The first bleeding episode was spontaneous in 10/19 (52.6%) and described as located in other, 42.1%, while 7/19 (36.8%) of patients experienced bleeds described as deep (musculoskeletal, retroperitoneal). The bleed characteristics of 14 patients with sufficient data are described in Table 1. The loading dose of rpFVIII administered ranged from 50 to 300 U/kg (mean 125.5 U/kg) to treat the bleeds, which significantly differs from the initial dose of 200 U/kg recommended in the Summary of Product Characteristics. Among the evaluable subjects for whom enough data has been collected, 14 bleeding episodes were resolved in 11 patients (11 initial bleeds, 2 subsequent bleeds and one (1) concurrent bleed), and five (5) bleeding episodes were not resolved in three (3) patients (3 initial bleeds and 2 subsequent bleeds). A mean of three (3) infusions (range: 1-46; median of 8.5) were required to resolved the bleeds for patients evaluable for efficacy at the time of this analysis, with an overall population mean of 6 infusions (range: 1-85; median of 13.3). Among the evaluable patients evaluable for treatment modality, six (6) were treated with rpFVIII as first line therapy for their initial bleeding event, and four (4) as first line for the subsequent bleeds. The remaining six (6) patients were treated with rpFVIII after other treatments as 2nd, 3rd or even 5th line therapy. To date, no thromboembolic events have been reported and one patient experienced a hypersensitivity reaction (rush). One therapy related serious adverse event was reported, a moderate vascular disorder (hemorrhage) considered "possibly related" to rpFVIII, which occurred more than 24 hours after the last treatment of rpFVIII.

Conclusions: From this preliminary data read out of the patients currently enrolled in the Post Marketing Surveillance study ongoing in the US, rpFVIII appears to be safe and effective in patients with AHA, a disease that is confirmed to occur in a very heterogeneous way. This study, along with a similar one in Europe, will provide a relevant amount of real world clinical data and may help with further assessment of the dosing regimen as well as guidance regarding appropriate dosing in order to personalize the treatment for each individual.

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