Regulatory Decision Summary for Trurapi

Trurapi (insulin aspart) is a biosimilar to the Canadian reference product NovoRapid (insulin aspart).

Comparable pharmacokinetics (PK) and pharmacodynamics (PD) between Trurapi and NovoRapid were established in a comparative pharmacokinetic and pharmacodynamic study conducted in patients with type 1 diabetes mellitus (T1DM). Pre-defined comparability margins of 80.0% to 125.0% for 90% and 95% confidence intervals (CIs) for PK and PD parameters, respectively, were met.

Non-clinical studies comparing Trurapi to reference products NovoRapid and NovoLog included pharmacodynamic and toxicology comparability studies. The weight of evidence supported the similarity of Trurapi with the reference product from a non-clinical perspective.

The efficacy and safety of Trurapi was compared to that of the reference product NovoRapid in a 26-week, open-label, randomized, active-controlled, study including 597 patients with T1DM or type 2 diabetes mellitus (T2DM).

Treatment with Trurapi provided a mean reduction in glycated hemoglobin (HbA1c) (primary efficacy endpoint) that was non-inferior to that achieved with the reference product. Fasting plasma glucose decreased from baseline to week 26 in both treatment groups and no differences were observed in the percentage of patients achieving a target HbA_1c <7%. The total daily doses of Trurapi and reference product were similar in the two treatment groups.

The types, frequency, and severity of adverse events were comparable between the Trurapi and the NovoRapid. The incidences of documented symptomatic hypoglycemia and severe hypoglycemia were similar in the two treatment groups. Two episodes of diabetic ketoacidosis were reported in the Trurapi group. Development of anti-insulin aspart antibodies was comparable in the two groups.

Overall, based on the totality of evidence derived from comparative structural, analytical and functional data, nonclinical data, and clinical data, similarity between Trurapi and NovoRapid has been demonstrated. The benefit/risk profile of Trurapi is considered to be similar to the reference product and favourable for the authorized indications.

Based on the evaluation of the data submitted, and as labelled, the Biologic and Radiopharmaceutical Drug Directorate (BRDD) considers that this New Drug Submission (NDS), control # 226573, for Trurapi indicated for the treatment of patients with diabetes mellitus who require insulin for the control of hyperglycemia, complies with the Food and Drug Regulations.

A Notice of Compliance has been granted.