Regulatory Decision Summary for Trazimera

Trazimera was developed as a biosimilar to the Canadian reference biologic drug, Herceptin (trastuzumab).

For the nonclinical and clinical review streams, the Sponsor submitted a nonclinical data package which included pharmacokinetic (PK), pharmacology, and toxicology program elements. In vitro primary biofunctional assays were also conducted as part of the analytical comparability package.

The clinical development program consisted of four studies:

• A pharmacokinetic (PK) study in healthy male volunteers demonstrated PK comparability between Trazimera and Herceptin. The 90% confidence intervals (CIs) of the PK parameters (AUC_T, and C_max [as point estimate]) were within the acceptance margins of 80.0% to 125.0%. The PK study was supported by additional PK-related data in the patient population.
• The main PK study was supported by an additional investigation in healthy volunteers focused on pyrexia assessment given observations noted in the PK study.
• A supportive pharmacokinetic assessment (primary endpoint) and included secondary efficacy endpoints as assessed in subjects with human epidermal growth factor receptor 2-positive (HER2+) early breast cancer (EBC) in the neoadjuvant setting. The analysis of the primary endpoint (PK) met the pre-specified non-inferiority criterion.
• In the main comparative clinical efficacy and safety study, no clinically meaningful differences between Trazimera and Herceptin were noted in HER2-positive metastatic breast cancer (MBC) patients in combination with paclitaxel. The primary efficacy analysis demonstrated that the 95% CI of the risk ratio of objective response rate (ORR) was contained within the pre-defined interval of 0.80 to 1.25 (0.940, 95% CI: 0.842, 1.049); furthermore, the risk difference of the ORR between the two treatment groups was also satisfactory. Secondary endpoints were supportive of the primary results, and the safety profiles were considered comparable.

A scientific rationale was provided to support the authorization of Trazimera in the proposed indications held by the reference product Herceptin, was considered in accordance with Health Canadas biosimilar guidance document, and is satisfactory.

The comparability of Trazimera to Herceptin was established based on comparative analytical and functional, non-clinical, pharmacokinetic (PK), and clinical studies.

Approved; issued Notice of Compliance in accordance with the Food and Drug Regulations.

For more information on Health Canadas decision, please view the Summary Basis of Decision.