Recombinant B-Domain Deleted Porcine Factor VIII (OBI-1) Safety and Efficacy in the Treatment of Acquired Hemophilia A: Interim Results.

Abstract

AbstractAbstract 2224 IntroductionOBI-1 is an investigational B-domain deleted recombinant porcine factor VIII (FVIII) with low cross-reactivity to anti-human FVIII antibodies. Acquired hemophilia A (AHA) is caused by autoantibodies (inhibitors) against human FVIII. Patients are predominantly elderly and have co-morbidities. Current pharmacologic treatment of bleeds is guided by clinical assessment alone as there is no laboratory surrogate for efficacy. Importantly, OBI-1 efficacy can be monitored by FVIII levels in addition to clinical assessment. MethodsAccur8 Auto-antibody trial (NCT01178294) is a prospective, open label, Phase 2/3 study. The primary objective is to evaluate efficacy of OBI-1 treatment for serious (life- or limb-threatening) bleeds in patients ≥18 years with AHA. FVIII levels are obtained before and within 10–20 min following initial OBI-1 dose (200U/kg) and at 2–3 h. Additional OBI-1 doses (≤400U/kg every 2–3 h) are administered to achieve target FVIII levels. The primary efficacy outcome is the control of bleeding 24 h after starting OBI-1. ResultsAs of July, 2012, fifteen patients with severe bleeds were entered into the trial along with one individual treated under compassionate use and all had successful control of hemorrhage at 24 h and subsequent resolution of the bleed. Therapeutic FVIII activity levels were achieved and maintained with intermittentOBI-1 administration based on FVIII levels. Six serious adverse events were reported including four deaths after treatment was discontinued, all being unrelated to OBI-1 as determined by the investigators. Antibodies to OBI-1 developed in two subjects indicated with an * in the table below. However, both responded toOBI-1.Sex (Age)Primary bleed siteAnti-human FVIII titer-pre-dose (BU)Anti-OBI-1 titer-pre-dose (BU)FVIII activity (%)24 h clinical outcome (hemostasis)Pre-first infusion20 min post-first infusion2-3 h post-first infusionM (72)1Surgical incision23Not detected9361186EffectiveF (82)Right knee/arm21Not detected1258230EffectiveM (43)Right arm (compartment syndrome)12Not detected18524601EffectiveM (91)Right deltoid (compartment syndrome)321013812EffectiveM (69)Left upper extremity swelling27Not detected22270233EffectiveM (66)*Interossei-dorsal of hand294Not detected1224164EffectiveF (73)Right thigh (surgical incision)124Not done0.37648EffectiveM (66)Hematoma of right upper extremity850.7111942EffectiveM (86)Upper limbs28Not detected9417278EffectiveF (79)Retroperitoneal hemorrhage651Not detected17720EffectiveF (81)Right iliacus muscle29210205EffectiveM (61)Surgical hemicolectomy36Not detected7296174EffectiveM (51)*Fundus of stomach16Not detected7240Not doneEffectiveF (64)Subcutaneous hematoma of left forearm11Not detected3288197EffectiveF (79)Left knee hemarthosis3Not detected14439331EffectiveF (82)Surgical tracheotomy290.9620982Effective1ompaidual treated under nate use individual1Compassionate use patient ConclusionsThese interim results provide support for the safety and efficacy of OBI-1 in the treatment of serious bleeding episodes in AHA. Additional confirming data could establish OBI-1 as a useful treatment option for AHA. Disclosures:St. Louis:Inspiration Biopharmaceuticals Inc: Research Funding. Kruse-Jarres:Inspiration Biopharmaceiticals Inc: Research Funding. Greist:Inspiration Biopharmaceuticals Inc: Research Funding. Shapiro:Inspiration Biopharmaceuticals Inc: Research Funding. Smith:Inspiration Biopharmaceuticals Inc: Research Funding. Drebes:Inspiration Biopharmaceuticals Inc: Research Funding. Gomperts:Inspiration Biopharmaceuticals Inc: Consultancy.