Regulatory Decision Summary for Semglee

The final decision for this New Drug Submission (NDS) was based on the totality of evidence, including structural, functional, non-clinical, pharmacokinetic/pharmacodynamic (PK/PD) and clinical comparisons.

The main Clinical study in this submission was a Phase 1 randomized, double-blind, single-dose, three-treatment, six period, six sequence, fully replicated, euglycemic glucose clamp study in 85 healthy subjects with the Primary Objective of assessing the comparative bioavailability of Semglee with the reference biologic product, Lantus. Pre-defined comparability margins of 80.0% to 125.0% for 90% confidence intervals (CIs) for Primary PK endpoint were met. Pre-defined comparability margins for the Primary PD endpoints based on pre-specified criteria for a highly variable drug product were also met.

Supportive Clinical Efficacy data was derived from a Phase 3 randomized, open-label, multi-centre trial, switching study, where 127 patients with Type 1 diabetes mellitus were randomized in a 1:1 fashion to either receive United States (US) Lantus consistently for a 36-week duration or to receive Semglee for a 12-week treatment period, followed by US Lantus for a 12-week treatment period, followed by a final Semglee 12-week treatment period. No clinically meaningful differences in efficacy were observed between the treatment group that switched between Semglee and US Lantus compared to the US Lantus only treatment group.

The safety profile of Semglee was consistent with the reference biologic drug, Lantus. No clinically meaningful imbalances were noted in the type, frequency, or severity of treatment emergent adverse events (TEAEs) or serious adverse events (SAEs) over the 36-week treatment period. No clinically relevant differences in the immunogenic profiles of Semglee and of Lantus were observed; anti-drug antibody titer did not correlate with changes in efficacy and the incidence of neutralizing antibodies was low.

Overall, based on the totality of evidence derived from the non-clinical and clinical data submitted in this NDS, the benefit/risk profile of Semglee is considered to be consistent to the reference product Lantus and is favourable for all the indications authorized for the reference biologic drug.

An updated Risk Management Plan (RMP) for Semglee was reviewed by Health Canada and considered acceptable.

For further details about Semglee, please refer to the Product Monograph, approved by Health Canada and available through the Drug Product Database.