Controversies in Care: The Evidence That Ang-2 Suppression Confers a Clinical Benefit

Is faricimab’s efficacy and extended durability due to its Ang-2 inhibiting properties, or simply the effect of a larger anti-VEGF dose?

By: Michael Colucciello, MD, Arshad M. Khanani, MD, MA, FASRS, Jennifer I. Lim, MD, FARVO, FASRS

Retinal Physician January 1, 2025 Vol 22, Issue January/February 2025 Page(s): 22-26

Clinical Report: Controversies in Care: The Evidence That Ang-2 Suppression Confers a Clinical Benefit

Overview

Revise to include specific studies that highlight the debate on Ang-2 inhibition versus anti-VEGF dosing.

Background

The treatment of neovascular age-related macular degeneration (nAMD) and diabetic macular edema (DME) has significantly improved with anti-VEGF therapies. However, challenges such as treatment adherence and resistance necessitate exploration of additional therapeutic pathways, including Ang-2 inhibition. Understanding the mechanisms behind these therapies is crucial for optimizing patient outcomes.

Data Highlights

No numerical data provided in the source material.

Key Findings

Faricimab, a bispecific antibody, targets both Ang-2 and VEGF-A, showing noninferior visual outcomes compared to aflibercept.
The RUBY study indicated no additional visual benefit from combining Ang-2 inhibitor nesvacumab with aflibercept, although anatomical improvements were noted.
In the YOSEMITE/RHINE trials, faricimab demonstrated sustained vision gains and improved anatomical outcomes over 24 months.
Approximately 80% of patients on faricimab were able to extend dosing to every 12 weeks, and 60% to every 16 weeks.
Elevated vitreous levels of Ang-2 are associated with several retinal diseases, suggesting a potential target for enhancing treatment efficacy.

Clinical Implications

Clinicians should consider the potential benefits of dual Ang-2 and VEGF-A inhibition in managing retinal diseases, particularly for patients who may benefit from extended treatment intervals. Ongoing assessment of anatomical and visual outcomes is essential to tailor therapy effectively.

Conclusion

The evidence surrounding Ang-2 suppression in retinal therapies highlights the complexity of treatment efficacy, necessitating further investigation to clarify its role relative to anti-VEGF dosing.

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