Regulatory Decision Summary for Ontruzant
Review decision
The Regulatory Decision Summary explains Health Canada’s decision for the product seeking market authorization. The Regulatory Decision Summary includes the purpose of the submission and the reason for the decision.
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What was the purpose of this submission?
Samsung filed a New Drug Submission for Ontruzant (trastuzumab, 440 mg/vial and 150 mg/vial, lyophilized powder for solution for intravenous infusion), a monoclonal antibody biosimilar to Herceptin (trastuzumab for injection, 440 mg/vial, the reference biological drug), for the indications held by Herceptin in Canada: HER2-positive early breast cancer, metastatic breast cancer and metastatic gastric cancer.
Why was the decision issued?
To support the biosimilarity of Ontruzant to Herceptin, comparative structural, functional, non-clinical, pharmacokinetic/pharmacodynamic (PK/PD) and clinical study results were provided.
The results of non-clinical studies, including pharmacodynamic, pharmacokinetic and toxicological studies, were considered satisfactory to the comparability of Ontruzant to Herceptin.
The results from a three-way, single-dose, parallel design study in healthy male subjects comparing PK profiles of Ontruzant to Herceptin (EU) showed that the point estimate for the Ontruzant and Herceptin (EU) geometric least square mean ratio for Cmax was 100.1 %, and the 90% confidence interval (CI) for geometric least square mean area under the concentration versus time curve at steady state (AUCT) was 91.1% - 103.4%. These results were within the equivalence margins of 80.0% to 125.0%; hence the comparable PK between Ontruzant and Herceptin-EU was demonstrated.
A randomised, double-blind comparative clinical study was conducted in patients with HER2-positive early breast cancer or locally advanced breast cancer to rule out any clinically meaningful differences between Ontruzant and EU-Herceptin with respect to safety, efficacy, or immunogenicity. The primary efficacy endpoint was breast pathological complete response (bpCR) after surgery following trastuzumab-containing neoadjuvant treatment. Based on the analysis in the intension-to-treat (ITT) population using non-responder imputation, the 95% CI for risk ratio (RR) for bpCR (RR: 1.243 [95% CI: 1.070, 1.444]) is fully contained within the pre-specified equivalence margins of 0.785 to 1.546. The safety profile observed was consistent with historical data on Herceptin in both neoadjuvant and adjuvant phases.
In accordance with Health Canadas biosimilar guidance document, a written scientific rationale was provided to support the authorization of Ontruzant in all the indications held by Herceptin, which was found satisfactory in the context of the demonstration of biosimilarity from a quality and clinical perspective.
The final decision for this product as based on the totality of evidence, including structural, functional, non-clinical, pharmacokinetic/pharmacodynamic (PK/PD) and clinical comparisons.
A Notice of Compliance (NOC) was recommended.
Decision issued
Approved; issued a Notice of Compliance in accordance with the Food and Drug Regulations