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The post hoc analysis of the phase 3 YOSEMITE/RHINE trials may support the therapeutic role of dual Ang-2/VEGF-A inhibition with faricimab for DME.
A post hoc analysis of the phase 3 YOSEMITE and RHINE trials revealed treatment with faricimab, a dual angiopoietin-2 (Ang-2)/vascular endothelial growth factor (VEGF)-A pathway inhibitor, led to greater resolution of hyperreflective foci compared with aflibercept, a VEGF-A inhibitor, in patients with diabetic macular edema (DME).
The analysis, presented at the 127th Annual American Academy of Ophthalmology (AAO) Meeting, showed greater HRF volume and count reductions at week 48, as well as faster time to the absence of HRF count, in faricimab-treated versus aflibercept-treated eyes.
“These findings support the therapeutic potential of dual Ang-2/VEGF-A inhibition with faricimab for patients with DME,” wrote the investigative team, led by Rishi Singh, MD, of the center for ophthalmic bioinformatics, Cole Eye Institute, Cleveland Clinic.
Among eyes with DME, hyperreflective foci may be considered a potential biomarker for disease severity and progression. Both Ang-2 and VEGF-A are primary drivers of vascular leakage, neovascularization, and inflammation in DME. In this analysis, Singh and colleagues compared the effect of faricimab, a dual Ang-2/VEGF-A inhibitor versus aflibercept, a VEGF-A inhibitor, on the resolution of retinal hyperreflective foci in eyes with DME to determine its effect on disease activity.
Within the analysis, spectral-domain optical coherence tomography (SD-OCT) volumes from 1527 patients in YOSEMITE and RHINE were automatically segmented using a deep learning-based algorithm trained with B-scans from the phase 2 BOULEVARD trial. Baseline hyperreflective volumes in the total retina
Upon analysis, Singh and colleagues observed greater reductions in hyperreflective foci counts in the inner retina with faricimab versus aflibercept (P <.001), at both the inner retina 1-mm and 3-mm diameter. They noted similar results were observed in the outer retina.
In addition, the analysis revealed greater reductions in hyperreflective foci volumes in the inner retina with faricimab versus aflibercept. At the 1-mm diameter, the adjusted mean hyperreflective foci volume reductions from baseline to week 48 were greater for every-8-week (Q8W) faricimab (–118.29 pL) and faricimab treat-and-extend (–130.05 pL) versus aflibercept (–58.67 pL; P = .0006 and P <.0001, respectively).
At the 3-mm diameter, the corresponding values from baseline to week 48 were similarly greater for faricimab Q8W (–406.76 pL) and faricimab treat-and-extend (–533.01 pL) versus aflibercept (–397.67 pL; P = .0142 and P = .0034, respectively). Singh and colleagues indicated that faricimab reduced hyperreflective foci volumes in the inner and outer retina – on the contrary, the effects of aflibercept were localized to the outer retina.
Moreover, faricimab demonstrated faster time to the absence of hyperreflective foci count at 2 consecutive visits in the inner and outer retina, compared with aflibercept. The 25th percentile in the inner retina 1-mm diameter was reached at approximately 36 weeks in the faricimab Q8W arm (hazard ratio [HR], 1.48; 95% CI, 1.21 - 1.82); P = .0002) and in the faricimab treat-and-extend arm (HR, 1.23; 95% CI, 1.00 - 1.52; P = .0487), compared to 44 weeks for aflibercept Q8W.
Meanwhile, the 50th percentile was reached at 32.1 weeks in the faricimab Q8W arm (HR, 1.45; 95% CI, 1.22 - 1.72; P <.0001) and 40.1 weeks in the faricimab treat-and-extend arm (HR, 1.24; 95% CI, 1.04 - 1.48; P = .0147), compared to 44.1 weeks for aflibercept Q8W.
Given these data, the investigative team noted faricimab resulted in greater resolution of hyperreflective focus versus aflibercept in patients with DME.
“Volumetric assessment of hyperreflective foci in YOSEMITE/RHINE demonstrated greater retinal hyperreflective foci volume and count reductions in faricimab- versus aflibercept-treated eyes to week 48,” investigators wrote.
Singh RP, Chakravarthy U., Maunz A., von Schulthess E., Patel K. et al. Automated Segmentation of Hyperreflective Foci in DME: Greater Volume Reduction with Faricimab in Phase 3 YOSEMITE/RHINE. Presented at the 2023 American Academy of Ophthalmology Annual Meeting, November 3 – 6, 2023.