Anti-Insulin Antibodies and Adverse Events with Biosimilar Insulin Lispro Compared with Humalog Insulin Lispro in People with Diabetes

Background: SAR342434 (SAR-Lis) is a biosimilar (follow-on) of insulin lispro (Humalog((R)); Ly-Lis). Two randomized, controlled, open-label, parallel-group, phase 3 studies were conducted to compare the efficacy and safety of SAR-Lis and Ly-Lis, both in combination with insulin glargine (Lantus((R))). SORELLA 1 was a 12-month study in 507 people with type 1 diabetes mellitus (T1DM); SORELLA 2 was a 6-month study in 505 people with type 2 diabetes mellitus (T2DM). In this study, the impact of anti-insulin antibodies (AIA) to SAR-Lis and Ly-Lis on safety and glycemic control is reported. Methods: AIA were measured regularly throughout both studies at a centralized laboratory blinded to treatment groups using a drug-specific AIA assay. The AIA status (positive or negative), AIA titers, and cross-reactivity to human insulin, insulin glargine, and insulin glargine metabolite M1 were analyzed. The potential effect of AIA on safety, particularly as related to hypersensitivity reactions, hypoglycemia, and treatment-emergent adverse events, as well as on glycemic control (HbA(1c), insulin dose), was evaluated. Results: AIA positive status at baseline was similar for the two insulins, but higher in T1DM than in T2DM. In both studies, the percentage of people newly developing AIA in the two treatment groups, or having a 4-fold increase in AIA titers, did not differ. No relationship was observed between maximum individual AIA titers and change in HbA(1c) or insulin dose, hypoglycemia, or hypersensitivity reactions or between efficacy/safety measures and subgroups by presence or absence of treatment-emergent AIA. Hypersensitivity events and events adjudicated as allergic reactions were few and did not differ between the two groups. Conclusion: Insulin lispro SAR342434 and the originator insulin lispro had a similar immunogenicity profile in people with T1DM or T2DM.