Greater reduction in hyperreflective foci with faricimab compared to aflibercept in patients with diabetic macular oedema

Abstract

Aims/Purpose: In diabetic macular oedema (DME), hyperreflective foci (HRF) may be a biomarker for disease severity and progression. This post hoc analysis aimed to test if faricimab, a dual‐action therapeutic inhibiting both vascular endothelial growth factor (VEGF)‐A and angiopoietin‐2 (Ang‐2), yields improved resolution of retinal HRF in DME compared to aflibercept.Methods: Phase 3 YOSEMITE/RHINE (NCT03622580/NCT03622593) spectral‐domain optical coherence tomography (SD‐OCT) volumes from 1527 DME patients were automatically segmented using a deep learning‐based HRF model trained with manually‐annotated B‐scans from phase 2 BOULEVARD (NCT02699450). Bright objects ≤50 μm in diameter were classified as retinal HRF. HRF volumes were assessed within the 1‐ and 3‐mm diameter Early Treatment Diabetic Retinopathy Study (ETDRS) rings, separated into inner and outer retina. Treatment groups were compared using a Mixed Model for Repeated Measures.Results: In the inner retina at 1 mm diameter, adjusted mean HRF volumes reduced more markedly from baseline to week 48 for faricimab every 8 weeks (Q8W; −118.29 pL) and faricimab treat&extend (T&E; −130.05 pL) than aflibercept Q8W (−58.67 pL; p = 0.0006 and p < 0.0001, for comparison of each faricimab arm vs aflibercept, averaged across all visits, respectively). In the inner retina at 3‐mm diameter, reductions from baseline to week 48 were − 406.76 pL (faricimab Q8W), −533.01 pL (faricimab T&E) and − 397.67 pL (aflibercept Q8W; p = 0.0142 and p = 0.0034, for comparison to aflibercept averaged across all visits, respectively). Similar, statistically significant results were obtained for the outer retina.Conclusions: Significantly greater retinal HRF volume reductions were observed with faricimab compared to aflibercept. Our findings of better resolution of the pathological manifestations of DME with faricimab support the therapeutic potential of dual Ang‐2/VEGF‐A inhibition.