326-OR: Faricimab for Diabetic Macular Edema: A Novel Anti–Angiopoietin-2/Anti–Vascular Endothelial Growth Factor Bispecific Antibody in Clinical Trials

In the United States, diabetic retinopathy (DR) and diabetic macular edema (DME) are a leading cause of blindness among working-age adults. The introduction of vascular endothelial growth factor-A (VEGF) inhibitors has improved the management of DME and allowed regression of DR severity. However, DR/DME is a multifactorial disease, and targeting additional pathways holds promise for better outcomes. Angiopoietin-2 (Ang-2) is upregulated in the eyes of patients with diabetes and promotes vascular destabilization and inflammation. Faricimab, a novel bispecific antibody targeting both Ang-2 and VEGF, was evaluated in the BOULEVARD (NCT02699450) phase 2 trial for DME. Patients (N = 168 treatment-naïve [TN]; N = 61 previously anti-VEGF treated) were randomized 1:1:1 to intravitreal ranibizumab 0.3 mg, faricimab 1.5 mg (TN only), or faricimab 6.0 mg, every 4 weeks for 20 weeks followed by 16 weeks of observation. BOULEVARD met its primary outcome: faricimab 6.0 mg achieved greater mean gains (letters) from baseline in best-corrected visual acuity than ranibizumab at week 24 in TN patients (faricimab 6.0 mg, +13.9; faricimab 1.5 mg, +11.7; ranibizumab, +10.3; faricimab 6.0 mg vs. ranibizumab, +3.6; P = 0.03; 80% CI, 1.5, 5.6). The Early Treatment Diabetic Retinopathy Study DR Severity Scale (DRSS) was used to score vascular abnormalities and disease severity on color fundus images. A change of ≥ 2 steps is considered clinically significant. The proportion of TN patients with ≥ 2-step improvement from baseline at week 24 on the DRSS was 38.6%, 27.7%, and 12.2%, respectively. There were no new or unexpected safety outcomes with faricimab. In conclusion, faricimab achieved better vision outcomes versus anti-VEGF monotherapy in TN patients, suggesting Ang-2 is a viable target for DR/DME. Phase 3 trials YOSEMITE (NCT03622580) and RHINE (NCT03622593) for faricimab in DME are ongoing. Disclosure V. Sheth: Consultant; Self; Genentech, Inc. J. Sahni: Employee; Self; Roche Pharma. Stock/Shareholder; Self; Roche Pharma. I. Stoilov: Employee; Self; Genentech, Inc. J.R. Willis: Employee; Self; Genentech, Inc. R. Weikert: Employee; Self; Roche Pharma. Funding F. Hoffmann-La Roche, Ltd.; Genentech, Inc.