Clinical evaluation of an advanced category recombinant FVIII, anti-hemophilic factor (recombinant) plasma/albumin-free method (rAHF-PFM) in surgical settings

Abstract number: P1643

Astermark^* J., Negrier† C., Schroth‡ P., Yi‡ S., Tonetta‡ S., Ewenstein‡ B.

‡Baxter BioScience, Westlake Village, CA, USA †Hôpital Edouard Herriot, Lyon, France; ^*University Hospital MAS, Malmo, Sweden;

The safety, immunogenicity and efficacy of Anti-hemophilic Factor (Recombinant), Plasma/Albumin-Free method (rAHF-PFM) was assessed in previously treated hemophilia A patients with baseline FVIII levels <=2% undergoing surgical, dental, or other invasive procedure in an on-going, open label Phase 2/3 clinical study. Data on the first 10 surgical procedures with rAHF-PFM, administered by bolus (n = 8) or continuous infusion (n = 2), are described here. Six subjects underwent major surgeries (5 orthopedic), which included one each of the following: total hip or knee joint replacement, arthrodesis, arthroscopic synovectomy/chondroplasty, synovectomy and transposition of an ulnar nerve. The remaining 4 subjects underwent minor surgeries, which included Mediport insertion and various dental extractions. A single preoperative loading dose of rAHF-PFM was administered to increase plasma FVIII levels to 60–100% of normal for dental procedures and 80–120% of normal for all other procedures. Target ranges were reached as expected and no supplemental loading doses of study drug were required in any subject. Intra- and postoperative hemostatic efficacy was rated as excellent/good in all 10 subjects and actual blood loss was as predicted for 9 of the 10 subjects. The predicted maximal blood loss was expected to be 2000 mL for one subject undergoing a total hip joint replacement with an actual blood loss of approximately 2900 mL assessed by the operating surgeon. Only this subject received blood products. No serious adverse events (SAEs) and no study drug-related AEs were reported; no inhibitors were detected in any subject. These data suggest that rAHF-PFM, an advanced category, full-length rFVIII prepared without the addition of human- or animal-derived raw materials in the cell culture, purification or formulation processes, is safe, effective and non-neoantigenic in the peri-operative management of patients with hemophilia A.