Faricimab causes rapid and sustained intraocular suppression of Ang-2 and VEGF-A for up to 16 weeks in nAMD and DME

Abstract

Purpose : Faricimab is a bispecific antibody designed to inhibit angiopoietin-2 (Ang-2) and vascular endothelial growth factor A (VEGF-A), promote vascular stability, and improve outcomes in neovascular age-related macular degeneration (nAMD) and diabetic macular edema (DME). The purpose of this analysis was to evaluate the intraocular pharmacodynamics of faricimab.

Methods : Optional aqueous humor (AH) samples were collected from patients in randomized, double-masked, active comparator–controlled, phase 2/3 trials in nAMD (AVENUE [NCT02484690], STAIRWAY [NCT03038880], TENAYA [NCT03823287], and LUCERNE [NCT03823300]) and DME (BOULEVARD [NCT02699450], YOSEMITE [NCT03622580], and RHINE [NCT03622593]). Free Ang-2 and VEGF-A levels were measured using validated assays. A population pharmacokinetic/pharmacodynamic model (popPKPD) was developed using phase 2/3 pooled data, including AH data from ~300 patients, corresponding to 1025 free Ang-2 concentrations, 1345 free VEGF-A concentrations, and 1095 faricimab concentrations. Only patients with at least 1 non–below the limit of quantification (BLQ) sample were included in the popPKPD analysis.

Results : Mean baseline VEGF-A levels were 135 pg/mL and 58 pg/mL in patients with DME and nAMD, respectively. Mean baseline Ang-2 levels were 13.4 pg/mL and 8.1 pg/mL in patients with DME and nAMD, respectively. Approximately 75% of post dose Ang-2 observations were BLQ. The popPKPD model described the observed data well. The model derived Ang-2 and VEGF-A concentration-time profiles showed that following intravitreal injection of faricimab, AH concentrations of Ang-2 and VEGF-A were rapidly suppressed to nearly unquantifiable levels. At 8 weeks post dose, median Ang-2 concentrations remained suppressed by ~80%. At 16 weeks post dose, median VEGF-A concentrations returned to baseline, but median Ang-2 levels remained below baseline.

Conclusions : PopPKPD analyses showed that faricimab treatment leads to rapid and sustained suppression of AH Ang-2 and VEGF-A levels, with Ang-2 suppression through 16 weeks post dose, supporting the extended durability demonstrated in phase 3 trials.

This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.