Perioperative Management of Hemostasis with Recombinant FIX Fc Fusion Protein in Subjects Undergoing Surgery in the B-YOND Study

Background: The phase 3 B-LONG (adults/adolescents ≥12 years of age) and Kids B-LONG (children Aims: To describe rFIXFc efficacy and safety in B-YOND subjects undergoing surgery. Methods: B-YOND subjects who underwent surgery received an investigator-determined rFIXFc regimen. Major surgery endpoints included rFIXFc dosing, investigator/surgeon assessment of hemostatic response (4-point scale: excellent, good, fair, poor/none), blood loss, number of transfusions, and safety. For minor surgeries, hemostatic response and dosing are summarized. Surgeries performed up to cutoff for the interim analysis (17 October 2014) were included. For safety analyses, the surgery subgroup included subjects who underwent major surgery during B-YOND and those who underwent major surgery in the parent study but had their surgical/rehabilitation period during B-YOND. Results: Fifteen major surgeries were performed in 8 subjects (7 adults/adolescents and 1 child Transfusion 2005;45:879). Hemostatic response for this surgery was rated as excellent. No subject reported a bleeding episode during the postoperative/rehabilitation period. Among 12 subjects in the surgery subgroup (8 with major surgery during B-YOND; 4 with major surgery in B-LONG and a surgical/rehabilitation period during B-YOND), 3 subjects (25%) reported ≥1 adverse event (AE) during the perioperative management period. One subject who underwent major surgery experienced 2 serious AEs (anal sphincter atony and epididymitis; considered unrelated to treatment) during the perioperative management period. All AEs were assessed by the investigator as unrelated to treatment and resolved. Of 25 minor surgeries performed in 17 adults/adolescents (none in children), approximately half were dental procedures (12/25 surgeries). No rFIXFc was administered on the day of surgery for 2 minor surgeries. For the other 23 surgeries, the median number of rFIXFc infusions was 1.0 (range, 1-3) and the median total dose of rFIXFc was 79.84 IU/kg (range, 38.5-200.0). Hemostatic response was assessed in 10 of 25 minor surgeries; all were rated as excellent (n = 9) or good (n = 1). Summary/Conclusion: Hemostasis with rFIXFc during surgery was rated favorably by investigators/surgeons, with comparable blood loss to what would be expected for subjects without hemophilia. Taken together with results from the B-LONG and Kids B-LONG studies, these data indicate that rFIXFc is well-tolerated and efficacious for the management of perioperative hemostasis in individuals with severe hemophilia B. Disclosures Ozelo: Baxter: Membership on an entity9s Board of Directors or advisory committees, Speakers Bureau; Novo Nordisk: Research Funding, Speakers Bureau; Biogen: Research Funding. Mahlangu: Bayer, CSL, Novo Nordisk, and Biogen: Research Funding, Speakers Bureau; Biotest: Speakers Bureau; Roche: Research Funding; Amgen: Speakers Bureau. Perry: Novo Nordisk: Consultancy, Membership on an entity9s Board of Directors or advisory committees; Biogen: Consultancy, Honoraria. Yuan: Biogen: Employment, Equity Ownership. Cristiano: Biogen: Employment, Equity Ownership. Mei: Biogen: Employment, Equity Ownership.