Introduction Haemophilia A or B patients with inhibitors have been treated with FVIIa‐containing bypassing agents for over 20 years. However, due to uncertainty regarding dose response and thrombotic risk, the use of a gradual, titrated, minimal dosing strategy remains prevalent, potentially hampering early haemostasis. Aim Evaluate the dose‐dependent efficacy, safety and immunogenicity of activated eptacog beta (rhFVIIa), a new recombinant inhibitor bypassing agent for the treatment of bleeding episodes (BEs). Methods A Phase 3, randomized, cross‐over study of initial dose regimens (IDRs) in 27 bleeding congenital haemophilia A or B subjects with inhibitors was conducted to evaluate on‐demand treatment of mild/moderate BEs. Intravenous 75 μg/kg or 225 μg/kg initial doses with 75 μg/kg subsequent doses by schedule were administered until clinical response. Results The primary endpoint was sustained clinical response within 12 hours, determined by a composite of objective and pain measures. In the 75 μg/kg IDR, 84.9% (95% CI; 74.0%, 95.7%) of mild/moderate BEs at 12 hours were successfully treated compared to 93.2% (95% CI; 88.1%, 98.3%) treated in the 225 μg/kg IDR. Efficacy between the IDRs was statistically different (P<.020) in mild/moderate bleeding episodes. Both IDRs were well tolerated with no detectable immunogenic or thrombotic responses to rhFVIIa or host cell proteins. Conclusion The dose‐dependent efficacy seen in this study supports individualizing the initial dose of eptacog beta to optimize clinical response. By reducing uncertainty, the PERSEPT 1 results should increase the adoption of early haemostasis as a treatment goal for clinicians who treat haemorrhage in the inhibitor population.

rThrombin or bThrombin used as a hemostatic ancillary for anastomotic bleeding was equally effective at 10 minutes; however, rThrombin compared with bThrombin may provide a more rapid onset of hemostasis at 3 minutes in PAB procedures. Adverse events were similar between the two thrombins. In patients undergoing vascular surgery, both treatments were similarly well tolerated, although rThrombin demonstrated a superior immunogenicity profile.

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Introduction: Haemophilia patients with inhibitors often require a bypassing agent (BPA) for bleeding episode management. Eptacog beta (EB) is a new FDA-approved recombinant activated human factor VII BPA for the treatment and control of bleeding in haemophilia A or B patients with inhibitors (≥12 years of age). We describe here the EB safety profile from the three prospective Phase 3 clinical trials performed to date. Aim: To assess EB safety, immunogenicity and thrombotic potential in children and adults who received EB for treatment of bleeding and perioperative care. Methods: Using a randomized crossover design, 27 subjects in PERSEPT 1 (12-54 years) and 25 subjects in PERSEPT 2 (1-11 years) treated bleeding episodes with 75 or 225 µg/kg EB initially followed by 75 µg/kg dosing at predefined intervals as determined by clinical response. Twelve PERSEPT 3 subjects (2-56 years) received an initial preoperative infusion of 75 µg/kg (minor procedures) or 200 µg/kg EB (major surgeries) with subsequent 75 µg/kg doses administered intraoperatively and post-operatively as indicated. Descriptive statistics were used for data analyses.Results: Sixty subjects who received 3388 EB doses in three trials were evaluated. EB was well tolerated, with no allergic, hypersensitivity, anaphylactic or thrombotic events reported and no neutralizing anti-EB antibodies detected. A death occurred during PERSEPT 3 and was determined to be unlikely related to EB treatment by the data monitoring committee. Conclusion:Results from all three Phase 3 trials establish an excellent safety profile of EB in haemophilia A or B patients with inhibitors for treatment of bleeding and perioperative use.

This study evaluated the safety, immunogenicity, and hemostatic effect of recombinant human Thrombin (rThrombin), in patients undergoing skin grafting for burns. This was a phase 2 multiple site, single-arm, open-label study in patients receiving partial- or full-thickness autologous grafts. rThrombin was applied using a spray applicator to newly excised wounds of 1 to 4% body surface area at 5 minutes intervals for up to 20 minutes, after point source bleeding was stopped. Adverse events, skin graft survival, and formation of anti-rThrombin antibodies were measured at baseline and Day 29. There were no deaths or study drug discontinuations. Adverse events occurred in 63 of 72 patients (88%), and were typical of sequelae of skin grafting. Hemostasis was achieved within 20 minutes after application of rThrombin in 65 of 71 patients (91.5%). Skin graft failure occurred in 4 patients (6%). At the day 29 evaluation, for those patients who returned, 88.9% had > or =90% graft survival. One patient (1 of 70, 1.4%) had specific, low titer antibodies to rThrombin at baseline, but no increase in titer posttreatment; a second patient (1 of 62, 1.6%), developed antibodies to rThrombin at day 29. None of the antibodies neutralized native human thrombin. In excised burn wounds, hemostasis at 20 minutes was achieved in 91.5% of patients and skin graft survival was excellent. There was a low rate of antibodies to rThrombin at baseline (1.4%) and a low rate of anti-rThrombin antibody formation at day 29 (1.6%). rThrombin was well tolerated when administered with a pump spray.