Proposed Aflibercept Biosimilar Shows Comparable Safety, Efficacy in Phase 3 AMD Trial

AVT06, a proposed biosimilar to aflibercept (Eylea; Regeneron Pharmaceuticals), demonstrated comparable efficacy, safety, and immunogenicity to the reference product in people with neovascular age-related macular degeneration (nAMD), according to a recently published phase 3 trial.¹ The findings may help expand patient access to vision-preserving therapies by supporting regulatory approval of a lower-cost alternative.

AVT06, a promising biosimilar to Eylea, shows comparable efficacy and safety for treating neovascular age-related macular degeneration (AMD), enhancing patient access. | Image credit: Coetzee/peopleimages.com - stock.adobe.com

The trial was designed to address the high cost of biologic therapies such as aflibercept, which remain a barrier for many patients worldwide. Researchers sought to determine whether AVT06 could match the clinical benefits of aflibercept, a mainstay of treatment for nAMD, while offering a potentially more sustainable option for health systems.

AVT06 is currently under review with the FDA and the European Medicines Agency (EMA), with the EMA’s Committee for Medicinal Products for Human Use adopting a positive opinion recommending approval of AVT06 for several indications, including nAMD, and the European Commission still left to make a final decision.^2,3

The study was a double-masked, randomized, parallel-group, multicenter investigation conducted across 117 sites in 14 countries between June 2022 and September 2024. A total of 410 participants, all aged 50 years or older and diagnosed with treatment-naive nAMD, were enrolled. Participants were randomized 1:1 to receive intravitreal injections of AVT06 or reference aflibercept (2 mg) over 48 weeks, with follow-up at Week 52.

The primary endpoint was the change in best-corrected visual acuity at Week 8, measured by Early Treatment Diabetic Retinopathy Study (ETDRS) letter scores. Both groups achieved clinically meaningful gains in vision, with AVT06 showing a least squares mean change of 5.11 letters compared with 4.34 letters in the aflibercept group. The difference of 0.77 letters fell well within the pre-specified equivalence margin of –3.5 to 3.5 letters, confirming comparable efficacy. Sensitivity analyses reinforced these results.

Secondary outcomes, including changes in central subfield thickness, lesion size, and the presence of intraretinal or subretinal fluid, were also similar between treatment arms through week 52. Both groups maintained consistent improvements in retinal anatomy and vision across all timepoints.

The pharmacokinetic substudy revealed comparable systemic exposure for both treatments, with overall low concentrations supporting systemic safety. Immunogenicity testing found that, although antidrug antibodies (ADAs) and neutralizing antibodies developed in some participants, the overall rates were low and consistent with aflibercept’s established profile. Interestingly, the proportion of ADA-positive participants was numerically lower in the AVT06 group compared with the reference arm by week 52 (66.8% vs 80.5%).

Safety findings further underscored comparability. The incidence of treatment-emergent adverse events (TEAEs) was similar between groups—67.8% in AVT06 and 56.1% in the aflibercept arm—with most events being mild, transient, and unrelated to study treatment. Severe TEAEs were reported in 2% of AVT06 participants and 4.9% of aflibercept participants. Three deaths occurred during the trial, none deemed related to study drugs. The most frequently reported adverse events were nasopharyngitis and ocular events such as conjunctival hemorrhage and cataract.

The participant population had a mean age of 74 years, with balanced gender distribution (53.4% female, 46.6% male). The majority of participants were White (76.1%), with 6.8% Japanese and 16.3% Asian. Most participants (85.4%) presented with unilateral nAMD, and baseline vision was moderately impaired, averaging 55 ETDRS letters. Disease characteristics, including the presence of intraretinal and subretinal fluid, were comparable across groups.

The authors acknowledged several limitations. As a tightly controlled clinical trial, the study may not fully reflect outcomes in real-world practice, where adherence and monitoring can differ significantly. Additionally, the trial was not designed to evaluate cost-effectiveness directly, though the biosimilar pathway inherently aims to improve affordability.

In discussing the implications of the findings, the study authors noted, “The primary outcome of this study supports the demonstration of comparable efficacy of AVT06 and reference aflibercept, contributing to the totality of evidence needed for biosimilar approval.” They added that the results provide a strong foundation for potential extrapolation to other aflibercept-approved indications, such as diabetic macular edema and retinal vein occlusion.

The study’s rigorous design, international scope, and comprehensive evaluation of visual function, retinal anatomy, pharmacokinetics, and safety lend credibility to the findings. If approved, AVT06 could represent a meaningful addition to the ophthalmology biosimilar landscape, helping reduce financial barriers to care and broadening treatment access for people with nAMD and related retinal diseases.

References

1. Agostini H, Baumane K, Balčiūnienė, et al. A randomized, double-masked parallel-group, multicenter clinical study evaluating the efficacy and safety of the biosimilar candidate AVT06 compared to the reference product aflibercept in participants with neovascular age-related macular degeneration. Expert Opin Biol Ther. 2025;25(7):773-787. doi:10.1080/14712598.2025.2519531

2. European Medicines Agency recommends market approval of AVT06, Alvotech’s proposed biosimilar to Eylea (aflibercept). News release. Alvotech. June 23, 2025. Accessed September 22, 2025. https://investors.alvotech.com/news-releases/news-release-details/european-medicines-agency-recommends-market-approval-avt06

3. Alvotech and Teva announce filing acceptance of U.S. biologics license application for AVT06, a proposed biosimilar to Eylea (aflibercept). News release. Alvotech. February 18, 2025. Accessed September 22, 2025. https://ir.tevapharm.com/news-and-events/press-releases/press-release-details/2025/Alvotech-and-Teva-Announce-Filing-Acceptance-ofU.S.-Biologics-License-Application-for-AVT06a-Proposed-Biosimilar-to-Eylea-aflibercept/default.aspx