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Recombinant Factor VIIa in Hemophilia
Studying the immunogenicity of vatrepacog alfa
Relatively small changes (3 amino acid substitutions) to the FVIIa molecule alter its clinical immunogenicity, according to a study of 72 patients with hemophilia A or B. Researchers found:
• 8 of 72 patients with inhibitors treated for acute bleeds developed antidrug antibodies (ADAs) to vatreptacog alfa.
• Immunoglobulin isotyping indicated that the ADAs were of the immunoglobulin G subtype.
• Epitope mapping confirmed that the antibodies were specific for vatreptacog alfa.
• In 2 patients, vatreptacog alfa showed a prolonged elimination phase following ADA development.
• During follow-up, the rFVIIa cross-reactivity disappeared after the last vatreptacog alfa exposure, despite continued exposure to rFVIIa as part of standard care.
Citation: Mahlangu JN, Weldingh KN, Lentz SR, et al. Changes in the amino acid sequence of the recombinant human factor VIIa analog, vatreptacog alfa, are associated with clinical immunogenicity. [Published online ahead of print October 13, 2015]. ]. J Thromb Haemost. doi: 10.1111/jth.13141.