LAUSR

Introduction: Anaphylaxis and severe hypersensitivity reactions are a concern for any biologic substance. The anti-IL-13 agent tralokinumab is produced by a murine cell line and may thus incorporate immunogenic α-Gal epitopes in the Fab domain. Objectives: 1) To identify possible events of anaphylaxis or severe hypersensitivity reactions in pivotal clinical studies of tralokinumab in severe, uncontrolled asthma. 2) To evaluate development of anti-drug antibodies (ADA) post dosing. 3) To characterize the glycosylation of tralokinumab and the presence of α-Gal epitopes in the Fab domain and Fc region. Methods: Drug safety was evaluated in the pivotal Phase III clinical studies (NCT02161757 and NCT02194699). Adverse events associated with anaphylaxis/hypersensitivity were captured with MedDRA SMQs: Hypersensitivity, Anaphylactic Reaction and Anaphylactic/Anaphylactoid Shock Conditions. Relevant cases were assessed by an independent expert for anaphylaxis (Sampson criteria). ADA and carbohydrate structure of tralokinumab were characterized by standard techniques. Results: Data from more than 1200 subjects indicate that there were no cases of anaphylaxis or severe hypersensitivity reactions related to tralokinumab administration. Less than 1% of the tralokinumab-treated subjects had ADA formation and no glycoforms with α-Gal epitopes were detected in the Fab region of the antibody. Conclusion: No safety concerns have been identified with respect to anaphylaxis/hypersensitivity and immunogenicity of tralokinumab in clinical studies. Tralokinumab is not considered to constitute an increased risk for anaphylaxis/hypersensitivity reactions by being manufactured in a murine cell line.