Immunate S/D – Results of a Phase III, Prospective, Multicenter Study to Evaluate the Pharmacokinetics, Immunogenicity, Safety, and Efficacy of Immunate Solvent Detergent in Previously Treated Patients with Severe or Moderately Severe Hemophilia A

Abstract number: P1231

Klukowska¹ A, Nemes² L, Lissitchkov³ T, Dobaczewski⁴ G, Komrska⁵ V, Fischer⁶ R, Auerswald⁷ G, Engl⁸ W, Hiebinger⁸ C, Abbühl⁸ B

¹¹Pediatric Clinic of Hematology and Oncology, Warsaw, Poland ²²National Hemophilia Center, Budapest, Hungary ³³National Centre of Hematology and Transfusion Medicine, Sofia, Bulgaria ⁴⁴Pediatric Clinic of Hematology and Oncology, Wroclaw, Poland ⁵⁵Children's Clinic, University Hospital Motol, Prague, Czech Republic ⁶⁶Kurpfalz Hospital Heidelberg, Heidelberg, Germany ⁷⁷Prof. Hess Children's Clinic, Bremen, Germany ⁸⁸Baxter Bioscience, Vienna, Austria ⁸⁸Baxter Bioscience, Vienna, Austria

IMMUNATE S/D is a plasma-derived FVIII-VWF complex in which the Polysorbate 80 treatment used in the production of IMMUNATE is replaced by solvent detergent (S/D) as a second viral inactivation step. This phase 3, prospective, multicenter study in 56 PTPs with severe hemophilia A (FVIII <= 1%) investigates immunogenicity, efficacy, and safety over a period of 27 weeks or 50 exposure days (ED) with IMMUNATE S/D. Treatment consisted of an on-demand or prophylactic regimen. Pharmacokinetic parameters were assessed in 18 subjects in a crossover comparison of IMMUNATE S/D and Immunate, and a reevaluation of IMMUNATE S/D after 14 weeks' treatment. IMMUNATE S/D was equivalent (80–125%, 90% CI) to IMMUNATE with respect to AUC_0–48 h, AUC_0-¥, t_1/2, CL, MRT, V_SS, C_max, T_max, and IR. After 14 weeks of treatment, repeat PK results showed no differences between the two IMMUNATE S/D infusions. The remaining samples were retrospectively assessed for the pharmacokinetic parameters of the VWF. Higher medians of IR and C_max were observed for VWF : Ag, VWF : CB and VWF : RCo with IMMUNATE S/D than with IMMUNATE. A normal number of multimers (14–26) was observed with each product. No inhibitors were detected in 2647 ED (mean = 47; range 17–76). A total of 623 bleeding episodes were reported in 47/56 subjects – 9 did not experience bleeding. Hemostatic efficacy was rated as excellent/good in 96% of all bleeds using a Global Assessment Score. Using the Global Assessment Score, 96% of the joint bleeds were rated as excellent or good compared to 99% when utilizing an Exploratory Scale designed to focus on the relative contribution of the number of infusions required, pain relief, and improvement in signs of bleeding. Only one possibly drug-related AE (mild infusion site pain) was reported. These results demonstrate that S/D treatment did not alter the excellent efficacy and safety profile of IMMUNATE.