Abstract
Abstract 2224
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.
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.
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 | 9 | 361 | 186 | Effective |
| F (82) | Right knee/arm | 21 | Not detected | 1 | 258 | 230 | Effective |
| M (43) | Right arm (compartment syndrome) | 12 | Not detected | 18 | 524 | 601 | Effective |
| M (91) | Right deltoid (compartment syndrome) | 32 | 10 | 1 | 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 | 1 | 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 | 1 | 119 | 42 | Effective |
| M (86) | Upper limbs | 28 | Not detected | 9 | 417 | 278 | Effective |
| F (79) | Retroperitoneal hemorrhage | 651 | Not detected | 1 | 77 | 20 | Effective |
| F (81) | Right iliacus muscle | 29 | 21 | 0 | 20 | 5 | Effective |
| M (61) | Surgical hemicolectomy | 36 | Not detected | 7 | 296 | 174 | Effective |
| M (51)* | Fundus of stomach | 16 | Not detected | 7 | 240 | Not done | Effective |
| F (64) | Subcutaneous hematoma of left forearm | 11 | Not detected | 3 | 288 | 197 | Effective |
| F (79) | Left knee hemarthosis | 3 | Not detected | 14 | 439 | 331 | Effective |
| F (82) | Surgical tracheotomy | 29 | 0.9 | 6 | 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 | 9 | 361 | 186 | Effective |
| F (82) | Right knee/arm | 21 | Not detected | 1 | 258 | 230 | Effective |
| M (43) | Right arm (compartment syndrome) | 12 | Not detected | 18 | 524 | 601 | Effective |
| M (91) | Right deltoid (compartment syndrome) | 32 | 10 | 1 | 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 | 1 | 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 | 1 | 119 | 42 | Effective |
| M (86) | Upper limbs | 28 | Not detected | 9 | 417 | 278 | Effective |
| F (79) | Retroperitoneal hemorrhage | 651 | Not detected | 1 | 77 | 20 | Effective |
| F (81) | Right iliacus muscle | 29 | 21 | 0 | 20 | 5 | Effective |
| M (61) | Surgical hemicolectomy | 36 | Not detected | 7 | 296 | 174 | Effective |
| M (51)* | Fundus of stomach | 16 | Not detected | 7 | 240 | Not done | Effective |
| F (64) | Subcutaneous hematoma of left forearm | 11 | Not detected | 3 | 288 | 197 | Effective |
| F (79) | Left knee hemarthosis | 3 | Not detected | 14 | 439 | 331 | Effective |
| F (82) | Surgical tracheotomy | 29 | 0.9 | 6 | 209 | 82 | Effective |
Compassionate use patient
1ompaidual treated under nate use individual
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.
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.
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