Abstract

Abstract 2224

Introduction

OBI-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.

Methods

Accur8 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.

Results

As 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 intermittent

OBI-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 site Anti-human FVIII titer-pre-dose (BU) Anti-OBI-1 titer-pre-dose (BU) FVIII activity (%) 24 h clinical outcome (hemostasis) 
Pre-first infusion 20 min post-first infusion 2-3 h post-first infusion 
M (72)1 Surgical incision 23 Not detected 361 186 Effective 
F (82) Right knee/arm 21 Not detected 258 230 Effective 
M (43) Right arm (compartment syndrome) 12 Not detected 18 524 601 Effective 
M (91) Right deltoid (compartment syndrome) 32 10 38 12 Effective 
M (69) Left upper extremity swelling 27 Not detected 22 270 233 Effective 
M (66)* Interossei-dorsal of hand 294 Not detected 224 164 Effective 
F (73) Right thigh (surgical incision) 124 Not done 0.3 76 48 Effective 
M (66) Hematoma of right upper extremity 85 0.7 119 42 Effective 
M (86) Upper limbs 28 Not detected 417 278 Effective 
F (79) Retroperitoneal hemorrhage 651 Not detected 77 20 Effective 
F (81) Right iliacus muscle 29 21 20 Effective 
M (61) Surgical hemicolectomy 36 Not detected 296 174 Effective 
M (51)* Fundus of stomach 16 Not detected 240 Not done Effective 
F (64) Subcutaneous hematoma of left forearm 11 Not detected 288 197 Effective 
F (79) Left knee hemarthosis Not detected 14 439 331 Effective 
F (82) Surgical tracheotomy 29 0.9 209 82 Effective 
Sex (Age) Primary bleed site Anti-human FVIII titer-pre-dose (BU) Anti-OBI-1 titer-pre-dose (BU) FVIII activity (%) 24 h clinical outcome (hemostasis) 
Pre-first infusion 20 min post-first infusion 2-3 h post-first infusion 
M (72)1 Surgical incision 23 Not detected 361 186 Effective 
F (82) Right knee/arm 21 Not detected 258 230 Effective 
M (43) Right arm (compartment syndrome) 12 Not detected 18 524 601 Effective 
M (91) Right deltoid (compartment syndrome) 32 10 38 12 Effective 
M (69) Left upper extremity swelling 27 Not detected 22 270 233 Effective 
M (66)* Interossei-dorsal of hand 294 Not detected 224 164 Effective 
F (73) Right thigh (surgical incision) 124 Not done 0.3 76 48 Effective 
M (66) Hematoma of right upper extremity 85 0.7 119 42 Effective 
M (86) Upper limbs 28 Not detected 417 278 Effective 
F (79) Retroperitoneal hemorrhage 651 Not detected 77 20 Effective 
F (81) Right iliacus muscle 29 21 20 Effective 
M (61) Surgical hemicolectomy 36 Not detected 296 174 Effective 
M (51)* Fundus of stomach 16 Not detected 240 Not done Effective 
F (64) Subcutaneous hematoma of left forearm 11 Not detected 288 197 Effective 
F (79) Left knee hemarthosis Not detected 14 439 331 Effective 
F (82) Surgical tracheotomy 29 0.9 209 82 Effective 
1

Compassionate use patient

1ompaidual treated under nate use individual

Conclusions

These 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.

Author notes

*

Asterisk with author names denotes non-ASH members.