Faricimab in Neovascular AMD Complicated by Pigment Epithelium Detachment: An AI-Assisted Evaluation of Early Morphological Changes.

INTRODUCTION: This study investigates the early temporal changes in pigment epithelial detachment (PED) morphology following treatment with faricimab in patients with neovascular age-related macular degeneration (nAMD). Utilizing an artificial intelligence (AI)-assisted approach, we provide a detailed quantification and characterization of the dynamics of these morphological changes. METHODS: A prospective observational study was conducted on 22 eyes from 22 treatment-naïve patients with nAMD-associated PED (presenting either type 1 or type 3 macular neovascularization). Participants were administered intravitreal faricimab (6 mg) at baseline and at days 30, 60, and 90. Comprehensive ophthalmic evaluations and spectral-domain optical coherence tomography (SD-OCT) imaging were conducted at baseline and at seven additional follow-up visits on days 1, 7, 14, 30, 60, 90, and 120. An AI-based automated segmentation algorithm was utilized to precisely quantify changes in PED volume, alongside intraretinal (IRF) and subretinal fluid (SRF) volumes, at each time point. RESULTS: Treatment with faricimab resulted in a significant reduction in mean PED volume, with an average decrease of 12% at day 1, 29% at day 7, 51% at day 14, 68% at day 30, 72% at day 60, 79% at day 90, and 84% at day 120 (p < 0.0001 for all time points). Similarly rapid and marked reductions were noted in both mean IRF (23.5% at day 1, 90.7% at day 14) and SRF (14.4% at day 1, 91.2% at day 14) volumes. The study also showed a statistically significant improvement in best-corrected visual acuity (BCVA) over the follow-up period, correlating with the reduction in PED volume. CONCLUSION: Faricimab demonstrates early and significant efficacy in improving PED architecture in patients with nAMD. The rapid morphological improvements observed in this study suggest faricimab may represent a valid therapeutic option for PEDs associated with nAMD.

Comprehensive Assessment of the Impact of Intravitreal Faricimab on Retinal Diseases: A Systematic Review, Meta-analysis, and Trial Sequential Analysis.

BACKGROUND: Faricimab stands as the inaugural and sole bispecific antibody approved by the US Food and Drug Administration (FDA) for intravitreal injection. Nonetheless, the efficacy and safety of intravitreal faricimab remained uncertain. OBJECTIVES: The purpose of this study was to evaluate faricimab. METHODS: This systematic review and meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines (CRD42023398320). Five databases (Pubmed, Embase, Web of science, Cochrane Library, ClinicalTrials gov) were searched. We calculated pooled standard mean difference or odds ratio with 95% confident interval under a random-effect model or fixed-effect model. Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) was employed to ascertain the reliability of the analyses. Trial sequential analysis was performed to gauge the statistical reliability of the data in the cumulative meta-analysis. RESULTS: 8 studies (3975 participants) were included. The use of faricimab was associated with central subfield thickness (CST) change, but no difference was found in other primary efficacy outcomes. Apart from that, a correlation was observed between the use of faricimab and the risk of vitreous floaters. Based on TSA, strong evidence indicates that compared to the control group, faricimab aided in reducing CST but increasing the risk of vitreous floaters. CONCLUSIONS: In this study, a correlation existed between the use of faricimab and a reduction in CST, indicating a superior therapeutic effect. Moreover, participants treated with faricimab demonstrated a higher risk of vitreous floaters. More randomized controlled trials are essential to further explore the efficacy and safety of faricimab.

Short-Term Clinical Outcomes of Patients with Diabetic Macular Edema Following a Therapy Switch to Faricimab.

Background: With this study, we investigate the short-term clinical outcomes of patients affected by diabetic macular edema (DME) after switching to intravitreal Faricimab (IVF) in a real-world setting. Methods: We conducted a retrospective chart review on all patients treated for DME with IVF who showed insufficient responses to prior anti-VEGF therapy. Data collected included baseline patient demographics, medical history, best-corrected visual acuity (BCVA), central retinal thickness (CRT) and central retinal volume (CRV). We analyzed functional and structural measures before and after IVF, compared baseline demographics and treatment factors between Faricimab-responders and reduced-responders and assessed influencing factors of the follow-up BCVA and CRT. Results: This study included 25 eyes from 16 patients. After switching to IVF, the mean BCVA showed no significant improvement, changing from 59.4 ± 13.4 Early Treatment of Diabetic Retinopathy Study (ETDRS) letters at baseline to 61.4 ± 12.8 ETDRS letters at follow-up (p = 0.26). CRT significantly reduced from 414.4 ± 126.3 µm to 353.3 ± 131.1 µm (p < 0.011), and the 3 mm CRV significantly decreased from 2.8 ± 0.5 mm3 to 2.6 ± 0.6 mm3 (p < 0.012). Seven patients met the responder criteria, exhibiting an improvement of at least 5 ETDRS letters and a simultaneous CRT reduction of at least 30 µm. Further analysis showed that higher BCVA at baseline (p < 0.001) was associated with better BCVA following IVF, while higher baseline CRT (p < 0.003), a higher number of prior anti-VEGF agents (p < 0.034) and prior corticosteroid injections (p < 0.019) were associated with greater CRT at follow-up. Conclusions: Following the initial IVF injection series, we observed a clear improvement of anatomical measures. No functional improvement was observed, although visual acuity remained stable. Higher baseline BCVA was associated with better post-IVF BCVA, while higher baseline CRT, a greater number of prior anti-VEGF agents and prior corticosteroid injections were linked to higher CRT post-IVF.

Long-acting delivery and therapies for neovascular age-related macular degeneration.

INTRODUCTION: Neovascular age-related macular degeneration (nAMD) represents a leading cause of severe visual impairment in individuals over 50 years of age in developed nations. Intravitreal anti-vascular endothelial growth factor (VEGF) injections have become the standard of care for treating nAMD; however, monthly or bimonthly dosing represents significant time and cost burden due to the disease's chronic nature and limited medication half-life. AREAS COVERED: This review summarizes innovative therapeutics and delivery methods for nAMD. Emerging methods for extended drug delivery include high molar concentration anti-VEGF drugs, intravitreal sustained-release polymers and devices, reservoirs for intravitreal delivery, suprachoroidal delivery of small molecular suspensions and gene therapy biofactories. In addition to VEGF-A, therapies targeting inhibition of VEGF-C and D, the angiopoetin-2 (Ang-2)/Tie-2 pathway, tyrosine kinases, and integrins are reviewed. EXPERT OPINION: The evolving therapeutic landscape of nAMD is rapidly expanding our toolkit for effective and durable treatment. Recent FDA approvals of faricimab (Vabysmo) and high-dose aflibercept (Eylea HD) for nAMD with potential extension of injection intervals up to four months have been promising developments for patients and providers alike. Further research and innovation, including novel delivery techniques and pharmacologic targets, is necessary to validate the efficacy of developing therapeutics and characterize real-world outcomes, demonstrating promise in expanding treatment durability.

Efficacy, durability, and safety of faricimab with extended dosing up to every 16 weeks in diabetic macular edema: 2-year results from the Japan subgroup of the phase 3 YOSEMITE trial.

PURPOSE: To evaluate the 2-year efficacy, durability, and safety of faricimab in patients with diabetic macular edema (DME) in the YOSEMITE Japan subgroup. STUDY DESIGN: YOSEMITE/RHINE (NCT03622580/NCT03622593) subgroup analysis: global, multicenter, randomized, double-masked, active-comparator-controlled, phase 3 faricimab trials. METHODS: Patients were randomized 1:1:1 to intravitreal faricimab 6.0 mg every 8 weeks (Q8W) and per treat-and-extend (T&E) dosing, or aflibercept 2.0 mg Q8W. Outcomes were assessed through year 2 for the YOSEMITE Japan subgroup (N = 60) and the pooled YOSEMITE/RHINE global cohort (N = 1891). RESULTS: In the YOSEMITE Japan subgroup, 21, 19, and 20 patients were randomized to faricimab Q8W, faricimab T&E, and aflibercept Q8W, respectively (632, 632, and 627 patients in the pooled YOSEMITE/RHINE cohort). Vision gains and anatomic improvements with faricimab at year 1 were maintained over 2 years and were generally consistent between groups. Mean best-corrected visual acuity changes from baseline at year 2 (weeks 92-100 average) for the YOSEMITE Japan subgroup were +12.5, +9.0, and +5.0 letters in the faricimab Q8W, faricimab T&E and aflibercept Q8W arms, respectively (+10.8, +10.4, and +10.3 letters in the pooled YOSEMITE/RHINE cohort). At week 96, 61.1% of the YOSEMITE Japan subgroup and 78.1% of the pooled YOSEMITE/RHINE cohort were on ≥ Q12W dosing. Faricimab was well-tolerated with a safety profile comparable with aflibercept. CONCLUSION: Faricimab up to Q16W offered durable vision gains and anatomic improvements up to 2 years in patients with DME in the YOSEMITE Japan subgroup. Outcomes were generally consistent with the pooled YOSEMITE/RHINE cohort.

Short-Term Comparison of Switching to Brolucizumab or Faricimab from Aflibercept in Neovascular AMD Patients.

Background and Objectives: In this study, our objective was to assess and compare the changes in visual and structural outcomes among patients with neovascular age-related macular degeneration (nAMD) who were switched from intravitreal aflibercept (IVA) to either intravitreal brolucizumab (IVBr) or intravitreal faricimab (IVF) injections in a clinical setting. Materials and Methods: This observational clinical study included 20 eyes of 20 patients switched to brolucizumab and 15 eyes of 14 patients switched to faricimab from aflibercept in eyes with nAMD. We measured the structural outcome (central macular thickness (CMT)) and the visual outcome (best-corrected visual acuity (BCVA); logMAR) as follows: just before the most recent IVA injection (B0), one month after the most recent IVA injection (B1), just before the first IVBr or IVF injection (A0), one month after (A1) and three months after (A3) the first IVBr or IVF injection. Results: BCVA showed significant improvement at A1 (0.25 ± 0.34) and at A3 (0.19 ± 0.24) compared to A0 (0.38 ± 0.35) in the IVBr group (p = 0.0156, p = 0.0166, respectively). CMT (µm) was significantly thinner at A1 (IVBr: 240.55 ± 51.82, IVF: 234.91 ± 47.29) and at A3 (IVBr: 243.21 ± 76.15, IVF: 250.50 ± 72.61) compared to at A0 (IVBr: 303.55 ± 79.18, IVF: 270.33 ± 77.62) in the IVBr group (A1: p = 0.0093, A3: p = 0.0026) and in the IVF group (A1: p = 0.0161, A3: p = 0.0093). There was no significant difference in BCVA and CMT improvement observed between two groups at any time point (p > 0.05 for all). Conclusions: Switching from aflibercept to either brolucizumab or faricimab has a significant anatomical effect in eyes with nAMD and both treatments appear to be effective short-term treatment options. There is a trend towards greater visual improvements and reductions in CMT with brolucizumab.

Three-month outcomes of treatment with faricimab or aflibercept for neovascular age-related macular degeneration: a propensity score matching study in a Japanese population.

PURPOSE: This study aimed to compare the treatment outcomes of patients with neovascular age-related macular degeneration (nAMD) who initially received faricimab or aflibercept treatment using propensity score matching (PSM) to align patient backgrounds. METHODS: Patients with treatment-naïve nAMD who received either faricimab or aflibercept for three consecutive monthly injections as the loading phase were enrolled in this study. In the 1:1 PSM, sex, age, best-corrected visual acuity (BCVA), central macular thickness (CMT), central choroidal thickness (CCT), and AMD subtypes in the pre-treatment state were selected as covariates. We examined the BCVA, CMT, CCT, and remaining fluid at 1-, 2-, and 3-month after the first injection. RESULTS: After PSM, 43 eyes were included in the faricimab and aflibercept group each. Both groups showed significant improvements in BCVA, CMT, and CCT at 1-, 2-, and 3-month after the initial injection compared with baseline. Meanwhile, no significant differences were observed between the two groups at any time point regarding BCVA, CMT, and CCT. At 1-month, 18.6% of patients in the faricimab group and 41.9% in the aflibercept group demonstrated residual subretinal fluid or intraretinal fluid, with a significant difference between the groups (P = 0.03). CONCLUSION: The BCVA improved after three loading injections of both faricimab and aflibercept. Faricimab may provide a favorable early treatment response in reducing subretinal fluid in a Japanese cohort.

Real-world efficacy of intravitreal faricimab for neovascular age-related macular degeneration: a systematic review.

BACKGROUND: To systematically review the real-world outcomes of intravitreal faricimab treatment in patients with neovascular age-related macular degeneration (nAMD) to evaluate its efficacy and safety in clinical settings. This study was conducted due to the need for real-world evidence to complement the findings from controlled clinical phase-III trials. METHODS: A systematic literature search was conducted on March 17, 2024, across 11 databases, utilizing search terms specifically tailored each database. All studies were reviewed qualitatively with specific focus on the outcomes of interest: the best-corrected visual acuity (BCVA), the central retina thickness (CRT), and the burden of therapy. RESULTS: We identified a total of 22 eligible studies of 1762 eyes from 1618 patients with nAMD. Studies reported that intravitreal faricimab injections maintained BCVA in patients with previously treated eyes and demonstrated statistically significant improvement in patients with treatment-naïve eyes. The CRT was reduced after intravitreal faricimab therapy. Faricimab was well-tolerated, with no significant safety concerns identified, and reduced the overall burden of therapy. CONCLUSION: Real-world studies corroborate the conclusions drawn from phase-III trials regarding faricimab treatment, demonstrating improvement in both visual and anatomical outcomes. Additionally, no significant safety issues were identified, as the treatment was generally well-tolerated and reduced the overall burden of therapy in the real-world settings.

Intra-Ocular Inflammation and Occlusive Retinal Vasculitis Following Intravitreal Injections of Faricimab: A Case Report.

PURPOSE: Faricimab is a bispecific antibody that inhibits angiopoietin-2 and vascular endothelial growth factor-A action and has been approved for the treatment of neovascular age-related macular degeneration and diabetic macular edema. Clinical trials have demonstrated its favorable safety profile. This report presents a case of intra-ocular inflammation and occlusive retinal vasculitis following a second intravitreal injection of faricimab. METHODS: A single case report was obtained from a tertiary referral center. RESULTS: A 73-year-old Asian man diagnosed with polypoidal choroidal vasculopathy presented with decreased vision in the left eye (OS) 2 weeks after the second faricimab administration. In the fourth week after the second faricimab injection, swept-source optical coherence tomography (OCT) revealed hyperreflective dots in the vitreous cavity, indicating vitreous cells. Color fundus photography showed new-onset perivenular hemorrhages and pallor of the inferonasal retina OS, of which OCT revealed retinal inner layer thickening, suggestive of retinal arteriolar occlusions. Retinal fluorescein angiography revealed delayed filling of the inferior temporal vein. The patient was diagnosed with intraocular inflammation and occlusive retinal vasculitis OS associated with repeated intravitreal faricimab administrations. Intravitreal dexamethasone implant was used instead of faricimab at this visit. CONCLUSIONS: The findings of this case hint towards the potential risk of retinal occlusive events associated with intravitreal faricimab injections.

Switch to faricimab after initial treatment with aflibercept in eyes with diabetic macular edema.

PURPOSE: To assess the effectiveness of a switch to faricimab in individuals affected by DME and previously treated with aflibercept. METHODS: In this retrospective, single-center study, DME patients previously treated with at least 3 injections of aflibercept then switched to faricimab were enrolled. Best corrected visual acuity (BCVA) and central subfield thickness (CST) were recorded at baseline, at the time of the switch and at 6 months follow-up. At transition to faricimab, patients were categorized as "good visual responders" (≥ 5 letters from baseline) or "poor visual responders" (< 5 letters), and as "good anatomical responders" (any reduction in edema compared to baseline) or "poor anatomical responders" (no reduction or worsening of edema). Changes in BCVA and CST were recorded at 6 months after the switch to faricimab. RESULTS: 100 eyes of 100 patients (61 female, 61%) were switched to faricimab after a mean of 6.8 ± 3.3 aflibercept injections. At the 6 months follow-up, only "poor visual responders" (N = 62) demonstrated a meaningful increase in BCVA (Δswitch-6M = + 5 letters; P = 0.007), coupled with a reduction in CST (Δswitch-6M = - 67.9 µm; P = 0.004); participants with "poor anatomical response" upon transitioning exhibited a significant functional gain (Δswitch-6M = + 4.5 letters; p = 0.05) but limited CST enhancements (Δswitch-6M = - 95.1 µm; p = 0.05). CONCLUSIONS: Faricimab shows a positive impact on anatomical and functional metrics in DME cases refractory to aflibercept.

Real-World Outcomes of a Loading Phase with Intravitreal Faricimab in Neovascular Age-Related Macular Degeneration (n-AMD) and Diabetic Macular Edema (DME).

INTRODUCTION: The aims of this work were to evaluate the real-world efficacy and safety of a loading dose of intravitreal faricimab in eyes with active neovascular age-related macular degeneration (n-AMD) or diabetic macular edema (DME) and to analyze the treatment outcome in relation to specific biomarkers. METHODS: Patients with active n-AMD or DME, treated with four monthly intravitreal injections of faricimab, were enrolled in this retrospective, uncontrolled study. Best-corrected visual acuity (BCVA), central subfield thickness (CST), presence of retinal fluid (RF) on optical coherence tomography (OCT), and adverse events were assessed at baseline and at weeks 4, 8, 12, and 16. Predefined biomarkers were evaluated at baseline (BL) and at last visit. RESULTS: Sixteen eyes of 15 patients with n-AMD (n-AMD group) and 15 eyes of 12 patients with DME (DME group) were included. Mean (± standard deviation) logarithm of minimum angle of resolution (logMAR) BL BCVA changed from 0.68 (± 0.43) to 0.53 (± 0.36; P = 0.13) and from 0.51 (± 0.34) to 0.32 (± 0.24; P: 0.048) at week 16 in n-AMD and DME group, respectively. A statistically significant mean CST reduction was reported in both groups at last visit (n-AMD: - 166.5 µm; P = 0.0009/DME: - 110.8 µm; P = 0.0086). Seventy-five and 33% of eyes with n-AMD and DME respectively achieved complete RF resolution at last visit. Subfoveal inner and outer retinal damage correlated with a lower final BCVA in n-AMD group. The presence of large (> 100 µm) juxtafoveal microaneurysms (MAs) was significantly correlated with a higher chance of residual fluid in eyes with DME. CONCLUSIONS: Both n-AMD and DME groups achieved satisfactory anatomical results after a loading-dose of intravitreal faricimab. BCVA improvement might be hampered by pre-existing retinal damage in eyes with n-AMD. Large, juxtafoveal MAs might represent a hallmark of a slower anatomical response to the treatment in eyes with DME.

Summary of Research: Cost­Effectiveness of Faricimab in the Treatment of Diabetic Macular Oedema (DMO): A UK Analysis.

This is a summary of the original article ?Cost­Effectiveness of Faricimab in the Treatment of Diabetic Macular Oedema (DMO): A UK Analysis". DMO, a serious eye condition that can lead to vision loss in people with diabetes, is a significant health concern and a lack of knowledge exists about the cost-effectiveness (the balance of a treatment's cost and its effectiveness) of new treatments. This research assessed the cost-effectiveness of a new medication named faricimab, using a mathematical model that simulated the progression of DMO and its treatment over 25 years. The model compared faricimab against relevant therapeutic alternatives for DMO in the UK, including ranibizumab, aflibercept, and bevacizumab. The research discovered that faricimab could offer improved vision results and be cost saving or cost-effective. It also suggested that faricimab could lessen the strain on healthcare services due to its less frequent dosing schedule. Overall, such findings suggest that faricimab is a promising new treatment option for DMO that could benefit patients and the healthcare system. This could have implications for future treatment guidelines and the management of DMO in clinical practice.

Efficacy of Faricimab versus Aflibercept in Diabetic Macular Edema in the 20/50 or Worse Vision Subgroup in Phase III YOSEMITE and RHINE Trials.

PURPOSE: Diabetic Retinopathy Clinical Research Network Protocol T suggests that the response to treatment among patients with diabetic macular edema (DME) may vary depending on baseline best-corrected visual acuity (BCVA). We evaluated the efficacy of faricimab 6 mg versus aflibercept 2 mg over 2 years in patients with DME and baseline BCVA of 20/50 or worse enrolled in faricimab phase III trials. DESIGN: YOSEMITE and RHINE were identically designed, multicenter, randomized, double-masked, active comparator-controlled, noninferiority trials. PARTICIPANTS: Adults ≥18 years of age with center-involving macular edema secondary to type 1 or 2 diabetes. METHODS: Patients were randomized to faricimab every 8 weeks (Q8W), faricimab personalized treat-and-extend (T&E) regimen, or aflibercept Q8W. Post hoc subgroup analyses were conducted using the intention-to-treat population with baseline BCVA of 20/50 or worse. MAIN OUTCOME MEASURES: Changes in ETDRS BCVA and central subfield thickness (CST) from baseline to years 1 and 2 were compared between treatment arms using mixed-model repeated measures analyses. RESULTS: In YOSEMITE and RHINE, respectively, 220 and 217 patients in the faricimab Q8W arm, 220 and 219 patients in the faricimab T&E arm, and 219 and 214 patients in the aflibercept Q8W arm showed baseline BCVA of 20/50 or worse. In both trials, mean change in ETDRS BCVA was comparable between treatments across trials at years 1 and 2. In YOSEMITE, adjusted mean change from baseline in CST (µm) at year 1 was greater with faricimab Q8W (-232.8; P < 0.0001) and faricimab T&E (-217.4; P = 0.0004) ) versus aflibercept Q8W (-190.4). In RHINE, this was faricimab Q8W (-214.2; P = 0.0006) and faricimab T&E (-206.6; P = 0.0116) versus aflibercept Q8W (-186.6). In both trials, change from baseline in CST at year 2 was greater with faricimab Q8W versus aflibercept. The median time to first CST of <325 µm and first absence of intraretinal fluid was shorter in the faricimab arms versus the aflibercept arm, with fewer injections on average. CONCLUSIONS: In patients with DME and baseline ETDRS BCVA of 20/50 or worse, faricimab treatment resulted in comparable visual acuity, greater reduction in retinal thickness, and fewer injections compared with aflibercept. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Faricimab for neovascular age-related macular degeneration and diabetic macular edema: from preclinical studies to phase 3 outcomes.

Intravitreal anti-vascular endothelial growth factor (VEGF) therapy is the standard of care for diabetic macular edema (DME) and neovascular age-related macular degeneration (nAMD); however, vision gains and anatomical improvements are not sustained over longer periods of treatment, suggesting other relevant targets may be needed to optimize treatments. Additionally, frequent intravitreal injections can prove a burden for patients and caregivers. Angiopoietin-2 (Ang-2) has been explored as an additional therapeutic target, due to the involvement of Ang-2 in DME and nAMD pathogenesis. Recent evidence supports the hypothesis that targeting both VEGF and Ang-2 may improve clinical outcomes in DME and nAMD compared with targeting VEGF alone by enhancing vascular stability, resulting in reduced macular leakage, prevention of neovascularization, and diminished inflammation. Faricimab, a novel bispecific antibody that targets VEGF-A and Ang-2, has been evaluated in clinical trials for DME (YOSEMITE/RHINE) and nAMD (TENAYA/LUCERNE). These trials evaluated faricimab against the anti-VEGFA/B and anti-placental growth factor fusion protein aflibercept, both administered by intravitreal injection. In addition to faricimab efficacy, safety, and pharmacokinetics, durability was evaluated during the trials using a treat-and-extend regimen. At 1 year, faricimab demonstrated non-inferior vision gains versus aflibercept across YOSEMITE/RHINE and TENAYA/LUCERNE. In YOSEMITE/RHINE, faricimab improved anatomic parameters versus aflibercept. Reduction of central subfield thickness (CST), and absence of both DME and intraretinal fluid were greater in faricimab- versus aflibercept-treated eyes. In TENAYA/LUCERNE, CST reductions were greater for faricimab than aflibercept at the end of the head-to-head phase (0-12 weeks), and were comparable with aflibercept at year 1, but with less frequent dosing. CST and vision gains were maintained during year 2 of both YOSEMITE/RHINE and TENAYA/LUCERNE. These findings suggest that dual Ang-2/VEGF-A pathway inhibition may result in greater disease control versus anti-VEGF alone, potentially addressing the unmet needs and reducing treatment burden, and improving real-world outcomes and compliance in retinal vascular diseases. Long-term extension studies (RHONE-X, AVONELLE-X) are ongoing. Current evidence suggests that dual inhibition with faricimab heralds the beginning of multitargeted treatment strategies inhibiting multiple, independent components of retinal pathology, with faricimab providing opportunities to reduce treatment burden and improve outcomes compared with anti-VEGF monotherapy.

Real-World Outcomes of Faricimab Treatment for Neovascular Age-Related Macular Degeneration and Diabetic Macular Edema.

Purpose: The purpose of this study was to assess preliminary real-world outcomes in neovascular age-related macular degeneration (nAMD) and diabetic macular edema (DME) treated with intravitreal faricimab. Patients and Methods: This was a retrospective, observational consecutive-case real-world study of patients with nAMD or DME initiated on intravitreal faricimab between November 2022 and April 2023. Treatment-naïve patients and patients previously treated with alternate anti-vascular endothelial growth factor (anti-VEGF) agents were initiated on an intended treatment plan of four monthly faricimab injections as a loading regime. Efficacy was assessed across four treatment groups. Primary outcomes assessed for both cohorts were changes in best corrected visual acuity (BCVA) and central subfield thickness (CST) on optical coherence tomography (OCT). Secondary outcomes were alterations in OCT-defined structural features. Results: From 127 patients, 146 eyes received at least one dose of faricimab. Mean BCVA, measured in Early Treatment of Diabetic Retinopathy Study (ETDRS) letters, from baseline to fifth visit increased from: 59.0±12.8 to 62.2±14.3 in treatment-naïve nAMD; 61.1±17.6 to 63.5±14.8 in previously-treated nAMD; 61.1±13.0 to 72.8±11.5 in treatment-naïve DME; and 60.8±14.6 to 63.3±15.6 in previously-treated DME. Mean CST reduced in all four treatment groups between initiation to final loading dose, from: 442.8±172.0µm to 305.2±117.0µm (p<0.0001) in treatment-naïve nAMD; 355.2±115.1µm to 297.9±92.54µm (p<0.0001) in previously-treated nAMD; 465.8±109.1µm to 343.1±100.3µm (p<0.0001) in treatment-naïve DME; and 492.5±133.1µm to 388.5±131.4µm (p<0.0001) in previously-treated DME. Conclusion: Real-world outcomes showed some improvement in BCVA and CST for nAMD and DME following faricimab administration, including in patients previously treated with other anti-VEGF agents. Further work involving larger cohorts over longer periods is required to determine whether improvement is maintained, and if intervals can be extended to match those observed in clinical trials.

Analysis of Choriocapillaris Reperfusion Topography Following Faricimab Treatment for Neovascular Age-Related Macular Degeneration in Therapy-Naïve Patients.

INTRODUCTION: To assess changes in choriocapillaris (CC) vascular density surrounding macular neovascularization (MNV) in treatment-naïve age-related macular degeneration (AMD) after faricimab application using optical coherence tomography angiography (OCTA). METHODS: Twenty-five eyes of 25 treatment-naïve individuals who underwent intravitreal faricimab injections for neovascular AMD (nAMD) with type 1 MNV were included. Spectral-domain optical coherence tomography (SD-OCT) images and en-face swept-source OCTA images were analyzed, and the percentage of CC flow deficit (FD%), FD average area (FDa) and FD number (FDn) in five progressive 20.0-µm-wide concentric rings (R1, R2, R3, R4 and R5) surrounding the dark halo around the MNV were calculated. Image acquisition was carried out prior to the first faricimab injection (T0) and 1 month after the injection (T1). RESULTS: The topographical sub-analysis revealed noteworthy changes in all rings at T1 compared to T0. There was a notable progressive reduction in FD% at T1 compared to T0 values across all rings, indicating a gradual CC reperfusion following anti-VEGF treatment. Additionally, the average size of FD decreased after the loading phase. Although not reaching statistical significance, there was a progressive reduction in the FDa across all rings. CONCLUSION: Our study highlights a CC FD reduction following the administration of three consecutive faricimab injections. This effect was detected in all rings surrounding the dark halo. These observations suggest a partial CC reperfusion surrounding the MNV, potentially serving as an indicator for disease regression.

Beyond VEGF: Angiopoietin-Tie Signaling Pathway in Diabetic Retinopathy.

Complications from diabetic retinopathy such as diabetic macular edema (DME) and proliferative diabetic retinopathy (PDR) constitute leading causes of preventable vision loss in working-age patients. Since vascular endothelial growth factor (VEGF) plays a major role in the pathogenesis of these complications, VEGF inhibitors have been the cornerstone of their treatment. Anti-VEGF monotherapy is an effective but burdensome treatment for DME. However, due to the intensive and burdensome treatment, most patients in routine clinical practice are undertreated, and therefore, their outcomes are compromised. Even in adequately treated patients, persistent DME is reported anywhere from 30% to 60% depending on the drug used. PDR is currently treated by anti-VEGF, panretinal photocoagulation (PRP) or a combination of both. Similarly, a number of eyes, despite these treatments, continue to progress to tractional retinal detachment and vitreous hemorrhage. Clearly there are other molecular pathways other than VEGF involved in the pathogenesis of DME and PDR. One of these pathways is the angiopoietin-Tie signaling pathway. Angiopoietin 1 (Ang1) plays a major role in maintaining vascular quiescence and stability. It acts as a molecular brake against vascular destabilization and inflammation that is usually promoted by angiopoietin 2 (Ang2). Several pathological conditions including chronic hyperglycemia lead to Ang2 upregulation. Recent regulatory approval of the bi-specific antibody, faricimab, may improve long term outcomes in DME. It targets both the Ang/Tie and VEGF pathways. The YOSEMITE and RHINE were multicenter, double-masked, randomized non-inferiority phase 3 clinical trials that compared faricimab to aflibercept in eyes with center-involved DME. At 12 months of follow-up, faricimab demonstrated non-inferior vision gains, improved anatomic outcomes and a potential for extended dosing when compared to aflibercept. The 2-year results of the YOSEMITE and RHINE trials demonstrated that the anatomic and functional results obtained at the 1 year follow-up were maintained. Short term outcomes of previously treated and treatment-naive eyes with DME that were treated with faricimab during routine clinical practice suggest a beneficial effect of faricimab over other agents. Targeting of Ang2 has been reported by several other means including VE-PTP inhibitors, integrin binding peptide and surrobodies.

Treatment Effects of Switching to Faricimab in Eyes with Diabetic Macular Edema Refractory to Aflibercept.

Background and Objectives: Faricimab is a vascular endothelial growth factor A and angiopoietin-2 bispecific antibody. It is a novel therapeutic approach distinct from previous anti-vascular endothelial growth factor agents. This study aimed to evaluate the efficacy of switching from aflibercept to faricimab in the treatment of diabetic macular edema (DME) refractory to aflibercept, with a specific focus on the resolution of macular edema. Materials and Methods: The medical records of 29 eyes of 21 patients with DME that were refractory to intravitreal injections of aflibercept (IVAs) and who had completed the clinical follow-up of at least four intravitreal injections of faricimab (IVFs) were reviewed. The central retinal thickness (CRT), best-corrected visual acuity (BCVA), and the mean period (weeks) until the next injection were measured after the second-to-last IVA, first-to-last IVA, last IVA, and first to fourth IVFs following the transition to IVF. Results: The mean time from the first IVF to the assessment of effectiveness was significantly shorter than the time to the last IVA; however, no significant difference was found in the time from the second, third, and fourth IVFs to the assessment. The mean CRTs after the first and second IVFs were not significantly different from the CRT after the last IVA, but the mean CRT after the third and fourth IVFs was significantly thinner than that after the last IVA (p = 0.0025 and p = 0.0076, respectively). The mean BCVAs after the third and fourth IVFs significantly improved compared with that after the last IVA (p = 0.0050 and p = 0.0052, respectively). Conclusions: When switching the treatment to IVF for eyes with IVA-resistant DME, better treatment outcomes are achieved if IVF is performed three or more times.

Real-World Weekly Efficacy Analysis of Faricimab in Patients with Age-Related Macular Degeneration.

Objectives: This study entailed a weekly analysis of real-world data (RWD) on the safety and efficacy of intravitreal (IVT) faricimab in neovascular age-related macular degeneration (nAMD). Methods: A retrospective, single-centre clinical trial was conducted at the Department of Ophthalmology, University Hospital Zurich, University of Zurich, Switzerland, approved by the Cantonal Ethics Committee of Zurich, Switzerland. Patients with nAMD were included. Data from patient charts and imaging were analysed. The safety and efficacy of the first faricimab injection were evaluated weekly until 4 weeks after injection. Results: Sixty-three eyes with a complete 4-week follow-up were enrolled. Six eyes were treatment-naïve; fifty-seven eyes were switched to faricimab from another treatment. Neither group showed signs of retinal vasculitis during the 4 weeks after injection. Central subfield thickness (CST) and volume (CSV) showed a statistically significant decrease compared to the baseline in the switched group (CST: p = 0.00383; CSV: p = 0.00702) after 4 weeks. The corrected visual acuity returned to the baseline level in both groups. The macular neovascularization area decreased in both groups, but this was not statistically significant. A complete resolution of sub- and intraretinal fluid after 4 weeks was found in 40% (switched) and 75% (naïve) of the treated patients. Conclusions: The weekly follow-ups reflect the structure-function relationship beginning with a fast functional improvement within two weeks after injection followed by a return to near-baseline levels after week 3. The first faricimab injection in our cohort showed a high safety profile and a statistically significant reduction in macular oedema in switched nAMD patients.