aflibercept

Overview

Aflibercept is a therapeutic biologic used primarily as an anti-angiogenic agent. It functions as a soluble decoy receptor that binds vascular endothelial growth factor (VEGF) ligands, thereby reducing VEGF-mediated signaling involved in pathological neovascularization and vascular permeability. In ophthalmology, this mechanism underlies its use in retinal diseases such as neovascular age-related macular degeneration (nAMD) and diabetic macular oedema, where excessive VEGF activity contributes to abnormal blood vessel growth and leakage.

Beyond eye disease, aflibercept has also been studied in oncology as part of anti-angiogenic treatment strategies, including combination regimens for metastatic colorectal cancer. Recent research continues to evaluate its comparative effectiveness, pharmacokinetics, biosimilar performance, and delivery systems designed to extend dosing intervals while maintaining efficacy and safety.

Role in Recent Research

Recent publications have focused on aflibercept in several clinically relevant contexts, especially ophthalmology.

One real-world study compared faricimab and aflibercept as second-line therapies for neovascular age-related macular degeneration. The stated aim was to assess comparative effectiveness in routine practice, reflecting ongoing interest in how aflibercept performs relative to newer anti-VEGF therapy options such as faricimab.

Another study examined the biological effects of aflibercept and faricimab on VEGF-A165-induced vascular permeability using human-derived endothelial cells. This head-to-head in vitro comparison reported that aflibercept and faricimab equipotently restored endothelial barrier function, supporting the idea that both agents can counteract VEGF-driven barrier disruption.

A pharmacometric analysis of intravitreal aflibercept drug products evaluated population pharmacokinetics across formulations. The study reported that a high-dose product delivering 8 mg aflibercept every 12 or 16 weeks after initial monthly dosing produced visual gains non-inferior to the 2 mg formulation given every 8 weeks after initial monthly dosing, with comparable safety and fewer injections over 96 weeks. This work is relevant to efforts to reduce treatment burden in chronic retinal disease.

Biosimilar development was also represented in a 20-week extension study of MYL-1701P, a biosimilar aflibercept product, in diabetic macular oedema. The extension followed participants from a 52-week global phase III trial and was designed to assess safety, efficacy, and immunogenicity. This indicates continued evaluation of biosimilar anti-VEGF options as alternatives to reference aflibercept.

Drug-delivery innovation was another theme. A materials science study described a visible light photo-cross-linked thermogel as a single-component hybrid supramolecular-covalent hydrogel for sustained drug release. In that system, aflibercept was used as the antivascular endothelial growth factor biologic released from an in situ cross-linked depot, with release prolonged for more than 3 months. The authors framed this as a potential improvement over monthly injection regimens used for diseases such as nAMD.

Aflibercept also appeared in an oncology trial in older adults or frail elderly patients with metastatic colorectal cancer. In that randomized phase 2 study, aflibercept and 5-FU were compared with FOLFOX as first-line treatment. The publication situates aflibercept within fluoropyrimidine-based and angiogenesis-inhibitor-based treatment strategies for frail patients, although the provided context does not include detailed outcome data.

Finally, a nationwide Japanese database analysis of intravitreal injections and anti-VEGF agent use from 2017 to 2022 found that aflibercept remained the predominant anti-VEGF agent. The study also noted diversification after the introduction of brolucizumab and faricimab, indicating that aflibercept continues to occupy a central position in real-world retinal therapy practice.

Key Publications

NEWJul Real-world comparison of faricimab and aflibercept as second-line therapies for neovascular age-related macular degeneration. (Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie, 2026, PMID 42390573): "To compare real-world effectiveness of faricimab versus aflibercept as second-line therapies for neovascular age-related macular degeneration (nAMD)."
NEWJul Aflibercept and Faricimab Equipotently Restore Endothelial Barrier Function. (Investigative ophthalmology & visual science, 2026, PMID 42390173): "To study the biological effects of aflibercept and faricimab on vascular endothelial growth factor (VEGF)-A165-induced vascular permeability in an in vitro head-to-head comparison using human-derived endothelial cells."
NEWJul Integrated Population Pharmacokinetic Analysis of Intravitreal Aflibercept Drug Products. (CPT: pharmacometrics & systems pharmacology, 2026, PMID 42381356): "A high-dose drug product (AFL-HD) using a formulation distinct from AFL-2 and delivering 8-mg aflibercept every 12 or 16 weeks (following initial monthly dosing) provided visual gains non-inferior to AFL-2 administered every 8 weeks (following initial monthly dosing) and comparable safety with fewer injections over 96 weeks."
Jun Safety and efficacy of biosimilar aflibercept MYL-1701P in diabetic macular oedema: 20-week extension results following the INSIGHT pivotal trial. (BMJ open ophthalmology, 2026, PMID 42373197): "To evaluate the safety, efficacy and immunogenicity of biosimilar aflibercept (MYL-1701P) in participants with diabetic macular oedema who completed the 52-week global phase III trial and were enrolled in an extension study."
May Visible Light Photo-Cross-Linked Thermogel─A Single-Component Hybrid Supramolecular-Covalent Hydrogel for Sustained Drug Release. (ACS applied materials & interfaces, 2026, PMID 42131985): "We show that these thermogels can be applied as an in situ cross-linked depot that allows the release of the antivascular endothelial growth factor biologic, Aflibercept, to be prolonged for more than 3 months, achieving a marked improvement over existing treatment regimens for diseases such as neovascular age-related macular degeneration that necessitate monthly injections."
May Aflibercept and 5-FU vs. FOLFOX as 1st line treatment for older adults or frail elderly patients with metastatic colorectal cancer - The randomized phase 2 AIO / IKF ELDERLY trial (AIO-KRK-0117 / IKF 629). (European journal of cancer (Oxford, England : 1990), 2026, PMID 41905242): "Fluoropyrimidines + angiogenesis inhibitor or dose-reduced doublets are used for (frail) elderly patients with metastatic colorectal cancer (mCRC)."
Jan Nationwide trends and regional variation in intravitreal injections and anti-VEGF agent use in Japan from 2017 to 2022: An analysis of the NDB Open Data. (PloS one, 2026, PMID 42096458): "Aflibercept remained the predominant anti-VEGF agent, with diversification after the introduction of brolucizumab (FY 2020) and faricimab (FY 2022)."