Regulatory Decision Summary for Yesafili

The purpose of this New Drug Submission (NDS) was to seek market authorization of Yesafili (aflibercept), as a biosimilar to Eylea, for use in the treatment of neovascular (wet) age-related macular degeneration (AMD), visual impairment due to diabetic macular edema (DME), macular edema secondary to central or branch retinal vein occlusion (CRVO/BRVO), or myopic choroidal neovascularization (myopic CNV).

The sponsor consented to information sharing between Health Canada and health technology assessment organizations as part of an aligned review pathway.

Yesafili contains the same active pharmaceutical ingredient, aflibercept, as the Canadian authorized reference product Eylea. Authorization was based on one Phase III, randomized, double-blind, parallel group, multicenter study comparing the efficacy, safety, immunogenicity and pharmacokinetics of Yesafili (M710) and Eylea in patients with diabetic macular edema (DME). Patients (n = 355) with DME received either Yesafili (M710) (n = 179) or Eylea (n = 176) into the studied eye via intravitreal (IVT) route every 4 weeks for the first 5 injections, followed by once every 8 weeks (with potential for optional 4 weekly doses). The primary efficacy endpoint was the change from baseline in best-corrected visual acuity (BCVA) at Week 8.

The results from the clinical comparative study demonstrated no clinically meaningful differences between Yesafili and Eylea in terms of efficacy, safety, and immunogenicity in patients with DME. Extrapolation to other sought indications, i.e. visual impairment due to age-related macular degeneration (AMD), macular edema secondary to central or branch retinal vein occlusion (CRVO/BRVO), or choroidal neovascularization (CNV), is based on adequate justifications from the sponsor, i.e. the same mechanism of action of aflibercept and the findings of consistent safety profiles across the indications currently approved for Eylea. The proposed dose regimens of Yesafili are the same as those for Eylea.

Overall, the benefit/risk profile of Yesafili was found to be comparable to the one of Eylea. The benefit/risk profile of Yesafili is therefore favourable for all the indications for which the sponsor is seeking authorization (i.e. AMD, CRVO, BRVO, DME and myopic CNV).

The final decision for this product was based on the totality of evidence, including structural, functional comparability and clinical similarity in efficacy, safety, and immunogenicity between Yesafili and Eylea. Therefore, a Notice of Compliance (NOC) was recommended.

A Risk Management Plan (RMP) for Yesafili was reviewed by Health Canada and considered acceptable.

The chemistry and manufacturing information submitted for Yesafili 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.

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