Interchangeable Aflibercept Biosimilar, Enzeevu, Comparable With Eylea for nAMD

Enzeevu (aflibercept-abzv), a biosimilar developed by Sandoz, demonstrated biosimilarity to reference aflibercept (Eylea) in patients with neovascular age-related macular degeneration (nAMD). | Image Credit: Orawan - stock.adobe.com

Enzeevu (aflibercept-abzv), a proposed biosimilar from Sandoz, matched reference aflibercept (Eylea) in efficacy, safety, and pharmacokinetics among patients with neovascular age-related macular degeneration (nAMD), according to a study published in Retina.¹

Inflammation, oxidative stress, and neovascularization of the retinal and subretinal spaces are symptoms of the chronic, progressive eye disease. Reduced vision loss and optimized visual quality of life are the overall treatment goals. The most benefits are seen when treating nAMD early, continuous, and timely.

More treatment options have been presented with the approval of anti–vascular endothelial growth factor (VEGF) biologic therapies like aflibercept, ranibizumab, brolucizumab, and faricimab. The aflibercept biosimilar, Enzeevu, is the fourth biosimilar referencing Eylea, having received approval in August 2024.² Enzeevu was granted interchangeability status, which allows it to be substituted in place of the reference aflibercept at the pharmacy level without provider permission.

The approval of aflibercept-abzv was based on the Mylight study (NCT04864834), a phase 3, prospective, double-masked, 2-arm, parallel trial.¹ The primary outcome was the average change from baseline in best-corrected visual acuity (BCVA) at week 8 of treatment between reference aflibercept and aflibercept-abzv. The secondary end points were anatomical outcomes, BCVA at weeks 24 and 52, safety, immunogenicity, and pharmacokinetics.

Participants were randomized across 103 sites in 16 countries across North America, Europe, Asia, and Australia for a 52-week study duration. There were 485 total participants who were randomized to receive either the Sandoz aflibercept (n = 245) or Eylea (n = 240).

Efficacy

At week 8, researchers observed a treatment difference in mean change from baseline in BCVA in the per-protocol set. The study showed a mean of –0.3 (90% CI, –1.5 to 1), which fell within the predefined FDA and European Medicines Agency equivalence margins (–3 and 3, and –3.5 and 3.5, respectively). The study results demonstrated comparable mean changes in BCVA scores between treatment groups at all other timepoints up to week 52. Comparable proportions of patients maintained vision in both the aflibercept-abzv and reference aflibercept groups (16.7% and 17.2%, respectively).

Additionally, the proportion of patients with moderate visual gains was comparable between aflibercept-abzv (20.3%) and reference aflibercept (23.8%). By week 52, intraretinal fluid was observed via optical coherence tomography in 23.9% of participants receiving aflibercept-abzv compared with 24.3% of those receiving reference aflibercept.

Safety

Similar rates of participants experienced at least 1 treatment-emergent adverse event (TEAE) in the aflibercept-abzv (73.4%) and reference aflibercept groups (72.5%). The frequency of TEAEs was also similar between the biosimilar aflibercept-abzv (2.5%) and the reference product (2.9%). TEAEs caused treatment discontinuation in 4.5% of the biosimilar group and 3.3% of the reference drug group. The rate of serious AEs was minimal and similar in both the biosimilar (16%) and reference product treatment arms (12.5%).

Immunogenicity and Pharmacokinetics

Although both groups included participants with preexisting antidrug antibodies (ADAs), most participants in both groups remained ADA negative throughout the study. Every participant who became ADA positive had also developed neutralizing antibodies. Systemic free aflibercept concentrations 24 hours post dose were low and comparable between both treatment groups.

Limitations

The study included mainly White European or American participants, resulting in limited racial and ethnic diversity, which potentially limits the results. The data also confirmed safety and efficacy of aflibercept-abzv up to a maximum of 52 weeks, leaving the long-term results 1 year post treatment unconfirmed. However, the equivalence between the drugs demonstrates the expected alignment in long-term treatment response.

The proposed biosimilar aflibercept expands access to anti-VEGF treatments for nAMD, aiming to improve outcomes and reduce drug costs for patients and health care systems amid a growing patient population.

“Proposed biosimilar aflibercept represents a proposed biosimilar medicine to reference aflibercept that may play a future role in supporting optimized care for patients with nAMD,” study authors concluded.

References

1. Bordon AF, Kaiser PK, Wolf A, et al. Efficacy and safety of the proposed biosimilar aflibercept, SDZ-AFL, in patients with neovascular age-related macular degeneration: 52-week results from the phase 3 mylight study. Retina. 2024;44(10):1704-1713. doi:10.1097/IAE.0000000000004174

2. Jeremias S. FDA approves biosimilar Enzeevu for eye conditions. The Center for Biosimilars^®. August 12, 2024. Accessed February 4, 2025. https://www.centerforbiosimilars.com/view/fda-approves-biosimilar-enzeevu-for-eye-conditions