Efficacy and safety of recombinant porcine factor VIII in Japanese patients with acquired hemophilia A

Abstract

Acquired hemophilia A (AHA) is a rare bleeding disorder caused by autoantibodies inhibiting human factor VIII (hFVIII). This phase II/III open-label study evaluated the safety and efficacy of recombinant porcine factor VIII (rpFVIII, susoctocog alfa) in adults with AHA and severe bleeding episodes in Japan (NCT04580407). The initial rpFVIII dose was 200 U/kg, with subsequent doses based on clinical measures including plasma FVIII activity. The primary efficacy endpoint was the proportion of severe bleeding episodes with a positive response to rpFVIII therapy 24 h after treatment initiation. Five patients were eligible for, and completed, rpFVIII treatment (age group: 60s-80s; median hFVIII inhibitor: 52 BU/mL; porcine FVIII [pFVIII] inhibitor: 3/5 patients). The median (range) total dose/patient was 548.4 (198-1803) U/kg with a median 3.0 infusions/patient. All patients responded positively to rpFVIII therapy at 24 h regardless of baseline pFVIII inhibitor status. rpFVIII treatment was well tolerated with no adverse events of special interest such as thromboembolic events or de novo pFVIII inhibitors. This study supports the use of rpFVIII as a novel therapy in the clinical management of patients with AHA in Japan. rpFVIII was approved for treating bleeding episodes in adults with AHA in Japan in 2024.

Keywords: Acquired hemophilia A; Factor VIII deficiency; Japanese patients; Recombinant porcine factor VIII.

Fig. 1

Individual patient inhibitor titers against hFVIII and pFVIII over the entire treatment period. Data show individual patient inhibitor titers against a hFVIII and b pFVIII. For pFVIII inhibitor titers, the lower limit of quantification was > 0.6 BU/mL (shown as 0.0 BU/mL in this figure). Baseline values were obtained on study day 1 (either at screening or at initial treatment dose) for all patients except for patient 3, whose baseline pFVIII measurement was obtained on study day − 2 (at screening). BU Bethesda unit, hFVIII human factor VIII, pFVIII porcine factor VIII

Fig. 2

Individual patient FVIII:C and aPTT over the entire treatment period. Dose (U/kg) and timing of rpFVIII treatment relative to the first dose of rpFVIII (0 h) are shown by arrows. For FVIII:C, the lower limit of quantification was ≤ 1% (shown as 0% in this figure). For aPTT, the upper limit of quantification was ≥ 170 s (shown as 170 s in this figure). Values at baseline (either at screening or initial treatment dose) are also shown for pFVIII inhibitor concentrations, aPTT and FVIII:C. aPTT activated partial thromboplastin time, BU Bethesda unit, d day, FVIII:C factor VIII activity, h hour, min minute, pFVIII porcine factor VIII, rpFVIII recombinant porcine factor VIII, s second