Regulatory Decision Summary for Ahzantive

The purpose of this new drug submission (NDS) is to seek market authorization for Ahzantive (aflibercept injection), a proposed biosimilar to the Canadian reference biologic drug Eylea, which has been authorized in Canada since 2012 (marketed by Bayer Inc).

The sponsor, Valorum Biologics, is seeking all the adult indications for Ahzantive currently held by Eylea. These indications include treatment of neovascular age-related macular degeneration (wet AMD), visual impairment due to macular edema secondary to central retinal vein occlusion (CRVO), visual impairment due to macular edema secondary to branch retinal vein occlusion (BRVO), diabetic macular edema (DME), and myopic choroidal neovascularization (CNV).

Ahzantive (aflibercept injection) is a biosimilar biologic drug to the Canadian Reference Biologic Drug (CRBD) Eylea. The sponsor sought all adult indications with the vial presentation currently held by the CRBD on the basis of biosimilarity.

The main clinical study submitted to support the authorization was a Phase 3 study (Study FYB203-03-01) performed in adult patients with wet age-related macular degeneration (AMD). In this clinical trial, European Union (EU) Eylea was nominated as the reference biologic drug. A Phase 1 comparative bioavailability study was not performed due to the invasiveness of the intravitreal injection. Instead, a subset of patients in the Phase 3 study was evaluated for pharmacokinetics.

Study FYB203-03-01 was a Phase 3, 56-week multicentre, randomized, double-masked, 2-arm parallel study designed to compare efficacy, safety and immunogenicity of Ahzantive to Eylea, in patients with AMD. The investigational products were administered by intravitreal injection at a 2 mg/0.05 mL dose. Subjects received either Ahzantive or Eylea once every 4 weeks at three subsequent visits (baseline, week 4 and week 8), thereafter once every 8 weeks until the last dose at Week 48. The primary efficacy endpoint was the change from baseline in best corrected visual area (BCVA) at Week 8. The 95.2% confidence interval (CI) of the difference in BCVA from baseline at Week 8 between Eylea and Ahzantive was wholly contained within the equivalence margin of ± 3.5 letters.

A consistent safety profile was observed between Ahzantive and Eylea. Systemic pharmacokinetics were also consistent between Ahzantive and Eylea based on descriptive analyses in a limited number of patients. No consistent imbalances in immunogenicity were observed between Ahzantive and Eylea.

Overall, the pharmacokinetic, efficacy, and safety results evaluated as part of this submission provide clinical support for the establishment of biosimilarity between Ahzantive and the CRBD Eylea. Therefore, a Notice of Compliance (NOC) was recommended.

The Marketed Health Products Directorate (MHPD) considered that the proposed Ahzantive EU-Risk Management Plan (RMP) version 1.0 and the Canadian-Specific Addendum version 0.3 are acceptable. The Ahzantive RMP is aligned with the most recent Canadian RMP of the reference product, Eylea.

The chemistry and manufacturing information submitted for Ahzantive has demonstrated that the drug substance and drug product have been well characterized and can be consistently manufactured to meet the approved specifications.

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

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