An Evaluation of Safety with an Extended Half-Life, Pegylated, Full-Length Recombinant Factor VIII (BAX 855) in the Treatment of 243 Patients with Hemophilia a
Authors: Engl Werner , Patrone Lisa , Jacqueline Dyck-Jones , Tangada Srilatha D. , Abbuehl Brigitt E. 
Published: October 2019

Abstract
BAX 855 is an extended half-life, pegylated full-length recombinant factor VIII (PEG-rFVIII) built on ADVATE and is approved for prophylaxis and the treatment of bleeding in hemophilia A. Safety data from 7 clinical studies were integrated to evaluate single, short-term, and long-term exposure with BAX 855. These clinical trials included the following patients: previously treated adult, adolescent, and pediatric patients (PTPs) and previously untreated patients (PUPs). Immunogenicity, adverse events (AEs), and clinical laboratory parameters were assessed during prophylaxis, treatment of bleeding, perioperative management, and PK evaluations. Of 243 patients, the mean ±SD (range) age was 23.4 ±15.84 (0-61) years, there was 1 female; 74.9% of patients were White, 21.4% were Asian, and 2.5% were Black. Overall, 97 million IUs of BAX 855 were infused, resulting in a median (Q1; Q3) of 111 (73-196) exposure days (EDs) per patient, which ranged from 1 to 322 EDs. No patient developed inhibitory antibodies to FVIII (≥0.6BU) at any time. The 95% confidence intervals for developing inhibitory antibodies based on exposure are as follows: 0-0.19 for 191 PTPs with ≥50 EDs, 0-0.027 for 135 patients with ≥100 EDs, 0-0.37 for 98 patients with ≥150 EDs, and 0-0.68 for 52 patients with ≥200 EDs. At the time of the last blood sample analyzed, no patient had any antibodies to CHO proteins or persistent binding antibodies to FVIII, PEG-FVIII, or PEG. Binding antibodies were either pre-existing (28 patients) or transient (13 patients). No conclusion can be drawn as yet for 5 patients who developed binding antibodies shortly before or at the data cut-off for the analysis. The presence of binding antibodies could not be correlated to an altered PK or impaired efficacy. The only AE considered related to BAX 855 occurring in ≥1% of patients was headache; other related AEs (nausea; diarrhea, flushing, rash, and hypersensitivity) were observed in <1% of patients. No SAEs related to the use of BAX 855 were reported. One PUP discontinued due to a treatment-related AE: a mild, non-serious AE of hypersensitivity (a rash), which resolved. In total, 819 AEs were reported in 182/243 subjects administered ≥1 BAX 855 infusion. The overall rate of AEs/infusion was 2.7% (819 AEs/30,865 infusions), for non-serious AEs 2.5% (773 AEs/30,865), and for serious AEs 0.1% (46/30,865). No trends were observed in laboratory parameters or in vital signs. This safety update for BAX 855 confirms that the safety profile of BAX 855 is consistent with the safety profile of ADVATE. Overall, short- and long-term treatment with BAX 855 was safe and well tolerated in 243 pediatric, adolescent and adult subjects with severe hemophilia A from 3 completed and 4 ongoing studies. As experience with BAX 855 grows, this integrated safety update continues to confirm the safe use of BAX 855 for prophylaxis, the treatment of bleeding episodes, and perioperative management.

Disclosures
Engl: Shire, formerly Baxalta and Baxter: Employment, Equity Ownership. Patrone:Shire, formerly Baxalta and Baxter: Employment, Equity Ownership. Jacqueline:Baxalta US Inc., now part of Shire: Employment, Equity Ownership. Tangada:Baxalta US Inc., now part of Shire: Employment, Equity Ownership. Abbuehl:Shire, formerly Baxalta and Baxter: Employment, Equity Ownership.