Immunogenicity profile of rurioctocog alfa pegol in previously treated patients with severe congenital hemophilia A

Abstract

Rurioctocog alfa pegol is an extended half-life full-length recombinant factor VIII (FVIII) bound to 20 kDa polyethylene glycol (PEG) that has been shown to be well tolerated and efficacious in the treatment and prevention of bleeding events in previously treated patients with severe hemophilia A. Here, we present a comprehensive analysis of immunogenicity data collected during 6 clinical studies of rurioctocog alfa pegol including a total of 360 unique previously treated patients with severe hemophilia A. The analysis included treatment-emerging FVIII neutralizing antibodies (FVIII inhibitors), pre-existing and treatment-emerging antibodies binding to FVIII, PEG-FVIII, or PEG, and treatment-emerging antibodies binding to Chinese hamster ovary host cell proteins. Moreover, the potential association between the presence of these binding antibodies and adverse events (AEs) observed in patients was investigated and the potential impact of these antibodies on the incremental recovery of rurioctocog alfa pegol in patients was analyzed. Overall, the data indicate that rurioctocog alfa pegol is not associated with any unexpected immunogenicity characteristics. One of the 360 patients developed a transient FVIII inhibitor with a titer of 0.6 BU/mL, which was not associated with any serious AEs. Antibodies binding to FVIII, PEG-FVIII, or PEG were not detected at the time when the inhibitor was present. Moreover, 54 of the 360 patients either entered the clinical studies with pre-existing binding antibodies or developed these antibodies after exposure to rurioctocog alfa pegol. These antibodies were transient in most patients and did not show any causal relationship to either AEs or spontaneous bleeding episodes.