Immunogenicity of BAX 855 in previously treated patients with congenital severe hemophilia A

F. M. Horling1, P. Allacher2, H. Koppensteiner1, W. Engl1, F. Scheiflinger1, B. Abbühl1, B. M. Reipert1 (1Vienna, Austria, 2Krems, Austria)

Bleeding Disorders - Clinical Studies
Date: 18.02.2017,
Time: 08:30 - 09:45

Objective: BAX 855 is an extended half-life recombinant human coagulation factor VIII modified with polyethylene glycol (PEG) (Turecek 2012). It was recently approved in the US and Japan for on-demand treatment of bleeding events and for prophylactic treatment for patients with congenital severe hemophilia A. The efficacy and safety of BAX 855 were extensively studied during clinical development (Konkle 2015). The assessment of BAX855 immunogenicity was of particular interest because the development of neutralizing antibodies (FVIII inhibitors) is the most serious complication following replacement therapies with FVIII products. To fully understand the potential of BAX855 to induce antibody responses, both FVIII inhibitors and total FVIII-binding antibodies as well as antibodies against PEG-FVIII and PEG were assessed.

Methods: The clinical protocols (NCT02585960, NCT02210091, NCT01736475, NCT01913405, NCT01945593, NCT01599819, NCT02615691) and the methods used for antibody analytics (Whelan 2013; Lubich 2016, Konkle 2015) were previously described. Correlation analyses were done to assess any potential correlation between the development of antibodies and potential adverse events.

Results: None of the 243 subjects (6 PUPs and 237 PTPs) included in the analysis developed FVIII inhibitors (≥ 0.6 BU/mL) A total of 44 subjects tested positive for binding antibodies against FVIII, PEG-FVIII or PEG at single time points. 28 of these 44 subjects showed pre-existing antibodies against FVIII, PEG-FVIII, or PEG prior to first exposure to BAX 855 which disappeared during the study. 13 subjects who tested negative at screening developed transient antibodies at one or two consecutive study visits after exposure to BAX 855 which were not detectable at subsequent visits. For five subjects the transient or persistent nature of antibody response cannot be evaluated at time point of data cut off. There was no confirmed causal relationship between the appearance of binding antibodies against FVIII, PEG or PEG-FVIII and adverse events, nor was there an impact on hemostatic efficacy in any of the 44 subjects.

Conclusion: Our data indicate that BAX855 did not show an increased risk for PTPs to develop FVIII inhibitors. The data suggest that BAX855 did not induce immune responses associated with impaired treatment efficacy or with altered PK parameters.