Efficacy and Safety of Biosimilar SAR342434 Insulin Lispro in Adults with Type 2 Diabetes, Also Using Insulin Glargine: SORELLA 2 Study.

Background: SAR342434 (SAR-Lis) is a biosimilar (follow-on) of insulin lispro (U100; Humalog((R)); Ly-Lis). This study aimed to show similar efficacy, safety, and immunogenicity of SAR-Lis versus Ly-Lis in adult patients with type 2 diabetes mellitus (T2DM) treated with multiple daily injections, while using insulin glargine (GLA-100; Lantus((R))) as basal insulin. Methods: SORELLA 2 was a 6-month, randomized, open-label, Phase 3 study (NCT02294474). Insulin doses were adjusted to achieve fasting and 2-h postprandial glucose targets according to American Diabetes Association guidelines. Primary endpoint was the HbA(1c) change from baseline to week 26 (tested for noninferiority of SAR-Lis vs. Ly-Lis with a margin of 0.3%). Secondary endpoints included fasting plasma glucose (FPG), seven-point self-monitored plasma glucose (SMPG) profiles, hypoglycemic events, treatment-emergent adverse events (TEAEs), and anti-insulin antibodies (AIA). Results: A total of 505 patients were randomized (1:1) to multiple daily injections of SAR-Lis (n=253) or Ly-Lis (n=252) plus once-daily GLA-100. Least square (LS) mean (standard error) change in HbA(1c) from baseline to week 26 was similar in both treatment groups (SAR-Lis, -0.92% [0.051] and Ly-Lis, -0.85% [0.051]). Noninferiority at prespecified 0.3% noninferiority margin was demonstrated (LS mean difference of SAR-Lis vs. Ly-Lis: -0.07% [95% CI: -0.215 to 0.067]) as was inverse noninferiority. Similar changes in FPG, seven-point SMPG profiles, including postprandial glucose excursions and mean glucose over 24h, and insulin dosages were observed in the two groups. Hypoglycemia, TEAEs, and AIA (incidence and prevalence) did not differ between groups. Conclusions: Results from this controlled study in patients with T2DM also using GLA-100 support similar efficacy and safety (including immunogenicity) of SAR-Lis and Ly-Lis.