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A post hoc analysis of the phase 3 YOSEMITE and RHINE trials found significantly more patients had leakage resolution with faricmab than with aflibercept at Week 16.
Dual angiopoietin-2/vascular endothelial growth factor (VEGF)-A inhibition with faricimab was linked to reduced macular leakage, as well as more patients achieving leakage resolution compared with aflibercept, in patients with diabetic macular edema (DME), in the head-to-head dosing phase of the phase 3 YOSEMITE and RHINE trials.1
This posthoc analysis, presented at the 127th Annual American Academy of Ophthalmology Congress in San Francisco, California, showed approximately 15% of patients treated with aflibercept every 8 weeks (Q8W) experienced macular leakage resolution, compared to approximately 28% of patients treated with faricimab Q8W or treat-and-extend.
“Early treatment with dual pathway inhibition may improve outcomes beyond anti-VEGF treatment alone,” wrote the investigative team, led by Anton Kolomeyer, MD, of NJ Retina.
The posthoc analysis of YOSEMITE and RHINE evaluated if dual Ang-2/VEGF-A inhibition with faricimab, the first bispecific antibody FDA-approved for the eye, improves macular leakage, a biomarker of vascular stability, compared with VEGF inhibition with aflibercept, among a population with DME. Macular leakage area assessments were performed by masked readers from the Wisconsin Reading Center. The area within the Early Treatment Diabetic Retinopathy Study (ETDRS) grid was assessed on FA images.
Kolomeyer noted that change in the macular leakage area in patients with DME correlates with functional and vision outcomes. Results from the RUBY trial showed reductions in macular leakage were associated with improved anatomic and vision outcomes, with a 0.7 letter increase for every 1 mm2 decrease in leakage area. The PANORAMA trial showed that increased macular leakage was associated with an increased risk of developing center-involved DME.
In the YOSEMITE and RHINE head-to-head dosing phase, patients with DME received faricimab 6.0 mg (n = 1216), faricimab treat-and-extend with 4 loading doses, or aflibercept 2.0 mg (n = 593) every 4 weeks to week 16 of the trials. For this analysis, the investigative team assessed the macular leakage area and the proportion of patients with resolution of macular leakage (0 - 1.0 mm2).
Upon analysis, investigators found the median macular leakage area was similar at baseline for faricimab versus aflibercept (24.58 mm2 versus 25.64 mm2; P = .7072). However, at week 16, the median macular leakage area was significantly lower for Q8W and treat-and-extend faricimab-treated arms (n = 1128) versus the aflibercept Q8W arm (n = 560) (3.59 mm2 vs. 7.62 mm2; P <.0001), a 53% difference. At week 16, significantly more patients had resolution of macular leakage with faricimab than with aflibercept (28.4% versus 15.2%; P <.0001).
Kolomeyer and colleagues also investigated how increasing the dose of anti-VEGF may influence macular leakage. To do so, the team measured aflibercept 2 mg Q8W (n = 1670, aflibercept 8 mg Q12W (n = 328), and aflibercept 8 mg Q16 W (n = 163). Their analysis showed the mean change in total area of fluorescein leakage at week 12 was –10.9 mm2 in the aflibercept 2 mg Q8W cohort, –10.0 mm2 in the aflibercept 8 mg Q12W cohort, and –11.8 in the aflibercept 8 mg Q16W cohort.
“Increasing the dose of aflibercept by 4 times did not improve the area of macular leakage,” investigators wrote.
Kolomeyer A., Eichenbaum DA., Sivaprasad S., Csaky KG, Benech AC., Wang T., Haskova Z., Amador MJ., Mar F. Faricimab Reduces Macular Leakage vs. Aflibercept in Patients With DME. Presented at the 2023 American Academy of Ophthalmology Annual Meeting, November 3 – 6, 2023.