Greater reduction in hard exudates with faricimab vs aflibercept in patients with DME: biomarker results from the phase 3 YOSEMITE/RHINE trials

Abstract

Purpose : Diabetic macular edema (DME) is characterized by increased vascular permeability and deposition of hard exudates (HE) in the retina. This exploratory analysis of the YOSEMITE (NCT03622580) and RHINE (NCT03622593) trials evaluated if dual angiopoietin-2 (Ang-2)/vascular endothelial growth factor-A (VEGF-A) inhibition with faricimab (FAR) could reduce HE vs VEGF inhibition alone with aflibercept (AFL) in patients with DME.

Methods : Patients with DME were randomized 1:1:1 to receive intravitreal injections of FAR (6.0 mg every 8 weeks [Q8W] or treat and extend [T&E]) or AFL (2.0 mg Q8W). The presence of HE was evaluated by a central reading center using color fundus photography (CFP) within the Early Treatment of Diabetic Retinopathy Study grid at the screening visit and weeks 16, 52, and 96. Assessments of ‘definite’ or ‘questionable’ were regarded as indicative of HE.

Results : Evaluation for HE was performed on 1870 patients (FAR Q8W, n = 626; FAR T&E, n = 628; AFL Q8W, n = 616). Across the 3 treatment arms a similar proportion of patients had HE at baseline (80.8–81.6%). The proportion of patients with HE decreased over time. In patients with HE at baseline, the proportion with HE at week 16 was similar between FAR and AFL treatment arms. Following patients with HE at baseline to weeks 52 and 96, fewer FAR Q8W and T&E patients had HE vs AFL patients (79.0%, 75.8% vs 86.2% and 52.8%, 55.9% vs 64.5%, respectively). This corresponded to a difference of –7.2% (95% CI, –12.2%, –2.2%; nominal P = 0.0058) and –10.5% (–15.6%, –5.4%; nominal P < 0.0001) for FAR Q8W and T&E over AFL at 52 weeks, and –11.7% (–18.6%, –4.8%; nominal P = 0.0013) and –8.9% (–15.7%, –2.1%; nominal P = 0.0124) at 96 weeks, respectively. CFP of exudates present at baseline and absent at week 96 for a patient case is shown in Figure 1. Retinal segmentation (Figure 2) and quantification of HE volume on optical coherence tomography will be presented.

Conclusions : Numerically greater reductions in HE were achieved with dual Ang-2/VEGF-A inhibition with FAR vs AFL. These findings may be a reflection of the improved vascular stability with dual Ang-2/VEGF inhibition as demonstrated in other biomarker analyses.

This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.

 

Figure 1

 

Figure 2