Efficacy and Safety of Faricimab in ALTIMETER: A Trial Exploring Biomarkers of Ang-2 Inhibition in Patients With DME

Abstract

Purpose : Results from the phase 3 YOSEMITE/RHINE trials (NCT03622580/NCT03622593) support the potential for dual angiopoietin-2 (Ang-2) and vascular endothelial growth factor (VEGF)-A pathway inhibition with faricimab to promote vascular stability and extend treatment durability for diabetic macular edema (DME). The phase 2b ALTIMETER study explored the associations between clinical endpoints, multimodal imaging assessments, and aqueous humor (AH) biomarker patterns in patients with DME treated with faricimab.

Methods : ALTIMETER (NCT04597918) was a 6-month, open-label, single-arm, exploratory study that enrolled treatment-naïve patients (aged ≥18 years) with DME. Patients received 6 doses of faricimab 6 mg every 4 weeks with a final visit at day 168. Exploratory endpoints included change from baseline over time in best-corrected visual acuity (BCVA), central subfield thickness (CST), intraretinal fluid (IRF), macular leakage on fluorescein angiography, multimodal imaging, and AH biomarker patterns. Exploratory endpoints were analyzed in the modified intent-to-treat (mITT) population, defined as patients who received any amount of study drug. Safety monitoring and assessments were performed.

Results : In total, 99 patients were enrolled and included in the mITT and safety populations; 90.9% (n=90) completed study treatment. Mean (SD) age was 59.5 (9.8) years and most patients were male (n=61, 61.6%) and white (n=86, 86.9%). At week 24, adjusted mean (95% CI) change from baseline in BCVA and CST (Figure 1) was +9.2 letters (7.5, 10.9) and −200.2 µm (−214.1, −186.2), respectively. At week 24, the median (range) change from baseline in IRF volume (3 mm diameter) was –343.3 nL (–1882.3, 81.5). Macular leakage area reduced following treatment with faricimab (median [range]: baseline, 28.6 mm² [1.7, 40.4]; week 20, 2.8 mm² [0, 38.6]; Figure 2). High macular leakage was associated with elevated Ang-2-related proteins and immune regulators at baseline, which reduced with faricimab. Faricimab was generally well-tolerated, and safety was consistent with the known safety profile.

Conclusions : At 6 months, patients treated with faricimab demonstrated meaningful improvements in vision and anatomic endpoints consistent with those in YOSEMITE/RHINE. Further exploratory analyses are planned to identify additional biomarkers of vascular instability that may improve with dual Ang-2/VEGF-A inhibition.

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