Regulatory Decision Summary for Opuviz

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 Opuviz (aflibercept), filed by Samsung Bioepis Co., Ltd., as a proposed biosimilar to the Canadian Reference Biologic Drug (CRBD) Eylea, which has been authorized in Canada since 2013.

The sponsor is seeking all the adult indications 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).

Opuviz (aflibercept) is a proposed biosimilar biologic drug to the CRBD Eylea. The sponsor sought all adult indications presentations currently held by the CRBD on the basis of biosimilarity.

The main clinical study submitted in the dossier was a Phase 3 study (Study SB15-3001) performed in adult patients with wet AMD. In this clinical trial, United States (US) 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 SB15-3001 was a Phase 3 randomized, active-controlled, double-blind study designed to compare the efficacy, pharmacokinetics, safety, and immunogenicity of Opuviz and Eylea. The investigational products were administered by intravitreal injection at a 2 mg/0.05 mL dose. Subjects received either Opuviz or Eylea once every 4 weeks for 3 months, then once every 8 weeks until the last dose at Week 48. At Week 32, subjects in the Eylea group were re-randomized to either continue receiving Eylea or transition to Opuviz. The primary efficacy endpoint was the change from baseline in best corrected visual area (BCVA) at Week 8. The 95% confidence interval (CI) of the difference in BCVA from baseline at Week 8 between Eylea and Opuviz was wholly contained within the equivalence margin of ± 3 letters.

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

Overall, the pharmacokinetic, efficacy, and safety results evaluated as part of this submission provide sufficient clinical support for the establishment of biosimilarity between Opuviz and the CRBD Eylea.

An updated Risk Management Plan (RMP) for Opuviz was reviewed by Health Canada and considered acceptable. Measures proposed in the Opuviz RMP are in line with the most recent Canadian RMP of the reference product, Eylea.

The provided quality data supports the assertion that Opuviz can be considered a biosimilar to the Canadian reference biologic drug, Eylea. The chemistry and manufacturing information submitted for Opuviz has demonstrated that the drug substance and drug product 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. The labelling material submitted met all applicable regulations and guidance.

Overall, the benefit-harm-uncertainty profile was favourable for Opuviz (aflibercept; 2 mg/0.05 mL) 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 Opuviz, please refer to the Product Monograph, approved by Health Canada and available through the Drug Product Database.