Clinical Outcomes of Faricimab in Patients with Previously Treated Neovascular Age-Related Macular Degeneration
May 2024
Joshua Uhr MD
Retinal & Ophthalmic Consultants
Northfield, NJ
In contrast to traditional intravitreal anti-VEGF medications, faricimab is a bispecific monoclonal antibody that targets two pathways involved in the pathogenesis of neovascular AMD (nAMD): VEGF-A and angiopoietin-2 (Ang-2). Inhibition of VEGF-A reduces endothelial cell proliferation, vascular permeability, and the drive for neovascularization. Inhibition of Ang-2 can increase vessel stability and decrease susceptibility to the effects of VEGF-A. It is thought that faricimab’s novel dual mechanism may increase nAMD treatment efficacy and durability compared to drugs that inhibit VEGF only. This study aimed to assess functional and anatomic outcomes in patients with nAMD who were switched to faricimab after prior treatment with traditional anti-VEGF medications.
The authors performed a single-center retrospective chart review of eyes with nAMD that achieved incomplete resolution of fibrovascular pigment epithelial detachment (PED), intraretinal fluid (IRF), and/or subretinal fluid (SRF) with traditional anti-VEGF agents and were subsequently switched to faricimab. All included eyes received 3 anti-VEGF injections prior to the switch to faricimab, and 4 intravitreal faricimab injections. Primary outcomes measures were best-corrected visual acuity (BCVA), maximum PED height, and central foveal thickness (CFT).
A total of 218 eyes from 191 patients were included. The mean number of traditional anti-VEGF injections received prior to the switch to faricimab was 34.2 injections, at a mean interval of 35.70 days immediately prior to the switch. The mean number of injections prior to the switch was 2.5 of bevacizumab, 19.3 of ranibizumab, and 20.8 of aflibercept. The mean number of faricimab injections was 5.1 injections, with a mean interval of 43.1 days between the third and fourth faricimab injection.
Functional outcomes:
The mean BCVA prior to switching was logMAR 0.58 (Snellen equivalent 20/76). Mean BCVA was 0.57 (Snellen 20/69) after 1 faricimab injection and 0.55 (Snellen 20/71) after 4 faricimab injections (not statistically significant).
Anatomic outcomes:
The mean maximum PED height improved from 195 mm prior to the switch to 174.6 mm after 1 faricimab injection (P<0.001) and to 165 mm after 4 faricimab injections (P <0.001). The mean CFT improved from 354.8 mm prior to the switch to 322.9 mm after 1 faricimab injection (P<0.001) and to 306.6 mm after 4 faricimab injections (P <0.001). The proportion of eyes with IRF improved from 36.7% prior to the switch to 26.6% after 1 faricimab injection (P<0.001) and to 24.8% after 4 faricimab injections (P <0.001). The proportion of eyes with SRF improved from 53.2% prior to the switch to 34.9% after 1 faricimab injection (P<0.001) and to 26.6% after 4 faricimab injections (P <0.001).
The authors point out several study limitations. There was no control group, making it difficult to draw definitive conclusions. There were no treatment naïve patients, and therefore the authors are unable to comment on how “real-world” treatment naïve patients respond to faricimab. The retrospective nature and short term follow up (approximately 160 days after switching to faricimab) also limit the ability to draw conclusions about how patients respond to faricimab long-term.
In conclusion, eyes previously receiving traditional anti-VEGF injections achieved significant anatomic improvement after switching to faricimab. Improvement was achieved after just 1 faricimab injection, with further improvement achieved after 4 injections. There was a slight trend towards improvement in visual acuity as well, although this was not statistically significant. The authors postulate that since this cohort was made up of eyes previously receiving intravitreal injections, there may have been a selection bias for treatment-resistant eyes which have already reached visual stability. These early data are encouraging that faricimab may enable nAMD patients already receiving anti-VEGF injections to achieve better and more durable outcomes.
