Regulatory Decision Summary for Herzuma

Herzuma (trastuzumab) is a humanized monoclonal antibody that selectively binds to the extracellular domain of the human epidermal growth factor receptor 2 (HER2). It was developed as a biosimilar to the Canadian reference biologic drug, Herceptin (trastuzumab).

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

The results from two comparative PK studies in healthy subjects showed that the point estimate for the Herzuma and Herceptin geometric least square mean ratio for C_max was 96.6% and 97.2%, for the primary and pilot studies, respectively and the 90% confidence interval (CI) for geometric least square mean ratio for the AUC_T was 92.9-106.2% and 88.8-104.9%, for the primary and pilot studies, respectively. These results were within the equivalence margins of 80.0% to 125.0%; hence the comparable PK between Herzuma and Herceptin was demonstrated.

In a randomized, double-blind study conducted in HER2-positive EBC patients, no clinically meaningful differences between Herzuma and Herceptin was observed in terms of efficacy, safety and immunogenicity. The primary efficacy endpoint was pathological complete response (pCR) during surgery after trastuzumab-containing neoadjuvant treatment. The 95% CI for the risk ratio of the pCR rates between treatment arms (0.7622 - 1.0981) was contained within the pre-defined equivalence margin (0.74 - 1.35). The safety profile observed was consistent with historical data on Herceptin and the concomitant chemotherapy administered in the study. Although numerical differences were seen in some adverse events between Herzuma and Herceptin, they were not considered clinically meaningful.

In accordance with Health Canadas biosimilar guidance document, a scientific rationale was provided to support the authorization of Herzuma in the proposed indications held by the reference product Herceptin, which was found satisfactory.

A Notice of Compliance (NOC) was recommended.