Low immunogenicity of insulin efsitora alfa in participants with type 1 and type 2 diabetes mellitus

Abstract

Aims: To evaluate treatment-emergent antidrug antibodies (TE ADA) in once-weekly basal insulin efsitora-treated participants with type 1 and type 2 diabetes mellitus (T1DM and T2DM) from 5 phase 3 clinical trials and their potential impact on pharmacokinetics, efficacy and safety. Materials and Methods: Serum samples were collected at baseline and throughout the studies. ADA were measured and characterised for their cross-reactivity to native insulin or ability to neutralise efsitora or endogenous insulin. ADA impact on the pharmacokinetics, efficacy and safety of efsitora was evaluated by comparing the clearance of efsitora, glycated haemoglobin (HbA1c) change from baseline at the primary endpoint, and incidence of treatment-emergent hypersensitivity reactions or injection site reactions by ADA status, respectively. Results: About 0.6% and 3.0% of efsitora-treated participants with T1DM (341) and T2DM (1861), respectively, developed TE ADA. Cross-reactive antibodies to native insulin and neutralising antibodies against efsitora and native insulin were observed in 1.7%, 1.1% and 0.8% of efsitora-treated participants with T2DM, respectively, but not in those with T1DM. Maximum ADA titres ranged from 1:40 to 1:81 920, with a median of 1:80. The clearance of efsitora was similar between baseline ADA+ and ADA− groups. TE ADA status did not significantly affect HbA1c reduction or cause hypersensitivity or injection site reactions in efsitora-treated participants. Conclusions: Efsitora caused an immunogenic response in up to 3.0% of participants with T1DM and T2DM. Descriptive analysis indicates that the immunogenicity of efsitora did not noticeably impact its pharmacokinetics, efficacy or safety. The molecular design of efsitora may contribute to its low immunogenicity.