Regulatory Decision Summary for Adheroza

The purpose of this New Drug Submission (NDS) was to obtain market authorization, pursuant to section C.08.004 of the Food and Drugs Regulations, for Adheroza, a biosimilar to the reference product Herceptin (trastuzumab), filed by Accord Healthcare Inc, for the indications currently held by Herceptin in Canada: HER2-positive early breast cancer (EBC), metastatic breast cancer (MBC) and metastatic gastric cancer (MGC).

To support the biosimilarity of Adheroza to Herceptin, comparative structural, functional, non-clinical, pharmacokinetic (PK) and clinical study results were provided.

Comparable pharmacokinetics between Adheroza and Herceptin sourced from Europe (EU) and the United States (US) were demonstrated in a single-dose, three-arm parallel pharmacokinetic (PK) study conducted in healthy male participants. The applicable PK parameters to demonstrate comparable PK (90% confidence intervals [CIs] of AUC_last and C_max [as point estimate]) were all within the equivalence margins of 80.0% to 125.0%.

A randomized, double-blind, comparative clinical study was conducted in patients with HER2-positive metastatic breast cancer to rule out any clinically meaningful differences between Adheroza and Herceptin-EU with respect to safety, efficacy or immunogenicity. The trial met the primary efficacy endpoint as the 95% confidence interval (CI) of the risk difference for the Objective Response Rate up to week 24 (-0.1 95% CI -7.0, 6.9) was fully contained within the pre-specified equivalence margin (-13.5%, 13.5%). No clinically meaningful differences in the comparative safety or immunogenicity assessment were identified.

In accordance with Health Canada's biosimilar guidance document, a scientific rationale was provided to support the authorization of Adheroza for all the indications held by Herceptin in Canada which was found satisfactory in the context of the demonstration of similarity from a quality and clinical perspective.

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

The chemistry and manufacturing information submitted for Adheroza has demonstrated that the drug substance and drug product can be consistently manufactured to meet the approved specifications.

Comparative bioavailability data was reviewed and demonstrated that the proposed biosimilar Adheroza, is highly biosimilar to the reference medicinal product, EU-sourced Herceptin, from a quality perspective.

Following review and requested revisions, the final labelling and Product Monograph were considered to be acceptable.

Overall, the benefit-harm-uncertainty profile was favourable for Adheroza 150 mg and 420 mg/vial for the approved indication when used under the conditions of use recommended in the approved Product Monograph. Therefore, a Notice of Compliance (NOC) was recommended.

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