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Sandoz Canada has launched a biosimilar referencing the anti–vascular endothelial growth factor (VEGF) agent Eylea (aflibercept), Enzeevum, in Canada. Health Canada authorized Enzeevu for all indications of the reference biologic, including neovascular (wet) age-related macular degeneration (AMD), macular edema secondary to central and branch retinal vein occlusion (CRVO/BRVO), diabetic macular edema (DME), and myopic choroidal neovascularization (CNV).1–3 This regulatory decision, affirmed through a comparative analytical and functional assessment, expands the therapeutic landscape in Canada for clinicians treating common vision-threatening retinal diseases.1,4
The clinical relevance for ophthalmologists lies in added treatment options that may support cost-effective care delivery and patient access without compromising expected clinical outcomes.1–3 While Eylea’s established efficacy and safety are well documented in large Phase 3 clinical trials for these indications,5–7 the introduction of biosimilar alternatives may have implications for prescribing patterns, drug procurement, and healthcare system sustainability.
Regulatory and Drug Overview
Enzeevu received its Notice of Compliance from Health Canada after a thorough biosimilarity assessment, which included an evaluation of physicochemical properties, functional assays, and comparative quality attributes versus the reference product Eylea. The Summary Basis of Decision indicates that despite minor differences in glycosylation patterns and impurity profiles, these variances are not expected to meaningfully impact clinical efficacy, pharmacokinetics, or safety.1,4 Health Canada’s approval aligns with established regulatory principles for biosimilars, wherein equivalence is determined through a “totality of evidence” approach encompassing analytical, nonclinical, and, as required, clinical data.1
In Canada and other regulated markets, multiple aflibercept biosimilars are now approved or in development; for example, Yesafili was the first biosimilar to Eylea authorized by Health Canada in 2025 and launched with provincial public funding in Ontario.2,3,8 Additionally, other manufacturers have received approvals for aflibercept biosimilars such as Eydenzelt under similar frameworks.8
Mechanism of Action and Clinical Background
Aflibercept is a recombinant fusion protein that functions as a soluble decoy receptor for VEGF-A, VEGF-B, and placental growth factor (PlGF), blocking ligand binding to VEGF receptors on endothelial cells in the retina. This inhibition reduces pathological angiogenesis and vascular permeability, the key pathophysiologic processes underlying neovascular AMD, DME, and retinal vein occlusion–associated macular edema.9
The reference product Eylea has been widely adopted since its initial regulatory approvals based on pivotal Phase 3 trials demonstrating significant improvements in best-corrected visual acuity (BCVA) and macular thickness versus control interventions in wet AMD and DME populations.5–7 Its safety profile includes risks inherent to intravitreal injections, such as endophthalmitis and retinal detachment, as well as intraocular inflammation, which clinicians must monitor in practice.10
Key facts
- Drug and class: Enzeevu (aflibercept), VEGF inhibitor biosimilar
- Indications: Wet AMD, visual impairment due to macular edema from CRVO/BRVO, DME, myopic CNV (Canadian approval) 1,3
- Regulatory action: Health Canada Notice of Compliance for biosimilarity to Eylea 1
- Mechanism: Soluble decoy receptor targeting VEGF-A/B and PlGF 9
- Efficacy: Biosimilarity supported by analytical and functional comparability; real-world clinical outcomes pending broader use 1
- Safety considerations: Intravitreal injection–associated risks; comparable immunogenicity and safety profile expected based on biosimilarity 1,12
- Status/Geography: Authorized in Canada; other aflibercept biosimilars authorized previously (Yesafili, Eydenzelt) 2,8
Clinical Context and Unmet Needs
Age-related macular degeneration and diabetic retinal diseases represent leading causes of visual impairment globally and within Canada, particularly among aging and diabetic populations.11 Conventional anti-VEGF therapies, including aflibercept, ranibizumab, and bevacizumab (off-label in some jurisdictions), have revolutionized outcomes but impose substantial economic burdens due to high drug costs and repeated intravitreal administrations.5–7,12 Real-world adherence challenges and disparities in access underline the need for diversified therapeutic options.
Biosimilars offer the potential for reduced acquisition costs while maintaining clinical effectiveness, which may facilitate broader access and resource optimization in publicly funded health systems. However, clinicians should interpret cost benefits within the context of individual patient response and long-term comparative effectiveness data.12
Interpretive Considerations
While the approval of Enzeevu reflects rigorous evaluation of biosimilarity, it is important to note that designation as a biosimilar does not imply interchangeability in all jurisdictions; Health Canada does not currently designate biosimilars as automatically substitutable at the pharmacy level.1 Clinicians should be familiar with provincial policies and institutional protocols governing substitution. Comparative head-to-head clinical outcomes versus the reference product in routine practice remain limited, and post-marketing surveillance will be essential to confirm real-world equivalence in diverse patient subgroups.
Moreover, while Eylea biosimilars aim to match efficacy and safety, individual clinical responses can vary, and some patients may require tailored management strategies, including alternate dosing intervals or switching between anti-VEGF agents based on disease activity.
Limitations and Next Steps
Health Canada’s decision for Enzeevu is grounded primarily in analytical and functional similarity rather than new phase 3 outcome data, which is consistent with biosimilar regulatory standards but may not fully address clinician questions about real-world effectiveness across all indications. Additionally, the cost structure and payer coverage for Enzeevu outside of formulary negotiations remain to be defined.
Ongoing pharmacovigilance and comparative effectiveness research will be important to monitor safety signals and inform evidence-based prescribing. Real-world registries and observational studies may further clarify the positioning of biosimilars relative to established anti-VEGF agents.
References
Regillo CD, et al. Ophthalmology clinical trials demonstrating efficacy of aflibercept in wet AMD.
Diabetic Macular Edema trials of aflibercept.
Eylea prescribing information and safety profile.
Epidemiology of retinal diseases and burden.
Aflibercept biosimilars systematic review. Ophthalmic Research / Journal;
