Four-Year Outcomes of Faricimab in Diabetic Macular Edema: Results from the RHONE-X Extension Trial.

In patients with diabetic macular edema (DME) from YOSEMITE/RHINE, dual angiopoietin-2/vascular endothelial growth factor-A (VEGF-A) inhibition with faricimab resulted in visual/anatomic improvements with extended dosing. The SWAN trial (jRCTs031230213) will assess the efficacy, durability, and safety of faricimab during the treatment maintenance phase in patients with DME using a treat-and-extend (T&E)-based regimen adapted to clinical practice and the characteristics of patients achieving extended dosing intervals. SWAN is a 2-year, open-label, single-arm, interventional, multicenter trial enrolling adults with center-involving DME. All patients will receive three initial faricimab 6.0 mg doses every 4 weeks (Q4W). From week 12 onwards, in patients without active DME, dosing intervals will be extended in 8-week increments up to Q24W. In contrast, patients with active DME (central subfield thickness [CST] >325 μm and intraretinal fluid [IRF] or subretinal fluid [SRF] resulting in vision loss/disease aggravation) will receive a dose within a day and the dosing interval will be shortened by 4 weeks to a minimum of Q8W relative to the previous dosing interval. Recruitment commenced in August 2023 across a planned 16 sites in Japan. The primary endpoint is change in best-corrected visual acuity (BCVA) from baseline at 1 year (averaged over weeks 52, 56, and 60). Key secondary endpoints include: change from baseline in BCVA, CST, and National Eye Institute Visual Function Questionnaire scores over time; proportion of patients with BCVA (decimal visual acuity) ≥0.5, ≥0.7, ≥1.0, or ≤0.1; proportion of patients with absence of DME, and IRF and/or SRF over time. Safety endpoints include incidence/severity of ocular/nonocular adverse events. The SWAN trial is expected to provide evidence to support individualized faricimab dosing regimens, with the potential to reduce the burden of frequent treatments on patients, caregivers, and healthcare systems.

PurposeIn patients with diabetic macular edema (DME) from YOSEMITE/RHINE, dual angiopoietin-2/vascular endothelial growth factor-A (VEGF-A) inhibition with faricimab resulted in visual/anatomic improvements with extended dosing. The SWAN trial (jRCTs031230213) will assess the efficacy, durability, and safety of faricimab during the treatment maintenance phase in patients with DME using a treat-and-extend (T&E)-based regimen adapted to clinical practice and the characteristics of patients achieving extended dosing intervals.MethodsSWAN is a 2-year, open-label, single-arm, interventional, multicenter trial enrolling adults with center-involving DME. All patients will receive three initial faricimab 6.0 mg doses every 4 weeks (Q4W). From week 12 onwards, in patients without active DME, dosing intervals will be extended in 8-week increments up to Q24W. In contrast, patients with active DME (central subfield thickness [CST] >325 μm and intraretinal fluid [IRF] or subretinal fluid [SRF] resulting in vision loss/disease aggravation) will receive a dose within a day and the dosing interval will be shortened by 4 weeks to a minimum of Q8W relative to the previous dosing interval. Recruitment commenced in August 2023 across a planned 16 sites in Japan.ResultsThe primary endpoint is change in best-corrected visual acuity (BCVA) from baseline at 1 year (averaged over weeks 52, 56, and 60). Key secondary endpoints include: change from baseline in BCVA, CST, and National Eye Institute Visual Function Questionnaire scores over time; proportion of patients with BCVA (decimal visual acuity) ≥0.5, ≥0.7, ≥1.0, or ≤0.1; proportion of patients with absence of DME, and IRF and/or SRF over time. Safety endpoints include incidence/severity of ocular/nonocular adverse events.ConclusionsThe SWAN trial is expected to provide evidence to support individualized faricimab dosing regimens, with the potential to reduce the burden of frequent treatments on patients, caregivers, and healthcare systems.

BackgroundTo evaluate the predictive effect of TCED-HFV grading and imaging biomarkers on anti-vascular endothelial growth factor (anti-VEGF) treatment in diabetic macular edema (DME).Methods81 eyes of 81 DME patients who were treated with anti-VEGF were included in this retrospective cohort study. All patients underwent a comprehensive ophthalmic examination at baseline and follow-up, including best-corrected visual acuity (BCVA), fundus photography, and spectral domain–optical coherence tomography (SD-OCT). Baseline imaging biomarkers were qualitatively and quantitatively graded according to the TCED-HFV classification protocol, and DME was divided into early stage, advanced stage, severe stage, and atrophy stage.ResultsSix months post treatment, central subfield thickness (CST) in 49 eyes (60.5%) had decreased by 10% from baseline, 30 eyes (37.0%) had achieved CST < 300 μm, and 45 eyes (55.6%) had BCVA improved by more than five letters. Multivariate regression analysis revealed that eyes with baseline CST ≥ 390 μm had a higher probability of ≥ 10% reduction in CST from baseline, and eyes with abundant hyperreflective dots (HRD) had a lower probability of 10% reduction in CST (all P < 0.05). Eyes with vitreomacular traction (VMT) or epiretinal membrane (ERM) at baseline were less likely to reach the end point of CST < 300 μm (P < 0.05). BCVA increases of more than five letters were less likely in eyes with baseline BCVA ≥ 69 letters, complete or partial destruction of ellipsoid zone (EZ) at baseline (all P < 0.05). TCED-HFV staging was negatively correlated with BCVA at both baseline and 6 months (Kendall’s tau-b=-0.39 and − 0.55, all P < 0.01). TCED-HFV staging was positively correlated with CST at 6 months (Kendall’s tau-b = 0.19, P = 0.049) and negatively correlated with the reduction of CST (Kendall’s tau-b=-0.32, P < 0.01).ConclusionThe TCED-HFV grading protocol facilitates a comprehensive assessment of DME severity, standardizes the grading of multiple imaging biomarkers, and predicts the anatomical and functional outcomes of anti-VEGF treatment.

ObjectiveTo compare different doses and dosing regimens of RC28-E, a novel bispecific antibody that simultaneously binds vascular endothelial growth factor-A (VEGF-A) and fibroblast growth factor-2 (FGF-2), with conbercept in patients...

Treatment of Diabetic Macular Edema with an Inhibitor of Vascular Endothelial-Protein Tyrosine Phosphatase That Activates Tie2

Simultaneous Inhibition of Angiopoietin-2 and Vascular Endothelial Growth Factor-A with Faricimab in Diabetic Macular Edema: BOULEVARD Phase 2 Randomized Trial

BALATON and COMINO: Phase III Randomized Clinical Trials of Faricimab for Retinal Vein Occlusion

A Phase II Randomized Clinical Trial of Intravitreal Bevacizumab for Diabetic Macular Edema

Two-Year Outcomes of the Ranibizumab for Edema of the mAcula in Diabetes (READ-2) Study

Diabetic Macular Edema Treated with Anti–Vascular Endothelial Growth Factor: Considerations Related to Nonimprovers

To evaluate the prognostic factors for short-term visual and anatomical improvement of intravitreal ranibizumab (IVR) for diabetic macular edema (DME). Fifty-one eyes from 35 patients that received three consecutive monthly IVR for DME with moderate visual loss were retrospectively recruited; all cases had their baseline best-corrected visual acuity (BCVA) between 20/400 and 20/40. BCVA and central subfield thickness (CST) at baseline and month 3 were collected. Linear mixed models were used to evaluate the prognostic factors for visual and anatomical improvement at month 3. Younger age, poorer baseline BCVA and proliferative diabetic retinopathy (PDR) were correlated with better visual improvement at month 3 (P=0.002, 0.0001 and 0.007, respectively). Thicker CST and the presence of subretinal fluid at baseline were correlated with a greater reduction in CST (P<0.0001 and P=0.018, respectively). The presence of epiretinal membrane or previous posterior subtenon injection of triamcinolone acetonide (PSTA) were associated with a smaller reduction in CST (P=0.029 and 0.018, respectively), but had no significant effects in visual improvement at month 3 (P>0.05 for both). For eyes with DME and moderate visual loss, those with younger age, poorer baseline BCVA or PDR tend to have better visual improvement after three consecutive monthly IVR. Epiretinal membrane or previous PSTA result in less resolution of CST, but do not significantly affect visual improvement.

To describe the study design of the POYANG study, an international, randomized, double-masked, multicenter, active comparator-controlled Phase 3 trial assessing the efficacy and safety of faricimab, a dual inhibitor of angiopoietin-2 (Ang-2) and vascular endothelial growth factor A (VEGF-A), in patients with choroidal neovascularization secondary to pathologic myopia (mCNV). Adult patients with treatment-naïve mCNV will be randomized 1:1 to receive either faricimab 6.0mg or ranibizumab 0.5mg. After an initial active intravitreal treatment administration at randomization (Day 1), subsequent treatment will be administered using a pro-re-nata (PRN) dosing regimen. Patients will be seen monthly over a 48-week study period and active study drug will be administered when protocol-defined retreatment criteria are met. Criteria are based on changes in best-corrected visual acuity (BCVA), central subfield thickness (CST) or examination findings consistent with mCNV activity. A sham procedure will be administered to patients at study visits when there is no active mCNV disease activity, in order to maintain masking. This study aims to recruit approximately 280 patients with mCNV from 11 countries in the Asia-Pacific and European regions. The primary endpoint is non-inferiority of faricimab versus ranibizumab in change from baseline in BCVA averaged over Weeks 4, 8 and 12. Secondary endpoints include change in CST over time and number of treatments required. Incidence and severity of ocular and non-ocular adverse events will be assessed. POYANG is a Phase 3 registrational trial investigating the efficacy and safety of faricimab in patients with choroidal neovascularization secondary to pathologic myopia.

IntroductionReducing intravitreal injection frequency while maintaining efficacy is a critical goal in alleviating the burden associated with anti-vascular endothelial growth factor (VEGF) therapy in patients with diabetic macular edema (DME) or neovascular age-related macular degeneration (nAMD). In clinical trials, aflibercept 8 mg and faricimab 6 mg administered at extended dosing intervals have demonstrated similar efficacy compared with aflibercept 2 mg, but with fewer injections. This network meta-analysis (NMA) indirectly compared numbers of injections and efficacy between aflibercept 8 mg and faricimab 6 mg administered according to a treat-and-extend (T&E)-based regimen in patients with DME or nAMD.MethodsA systematic literature review was conducted on 10 January 2025, to identify randomized controlled trials of aflibercept 8 mg or faricimab T&E with observation periods of approximately 2 years. Outcomes included number of injections, absolute change from baseline in best-corrected visual acuity (BCVA), and absolute and percentage change from baseline in central subfield thickness (CST). NMAs were performed with Bayesian statistical models. Injection numbers were adjusted to 104 weeks to account for differences in trial observation periods.ResultsThe NMA included 2-year data from six trials: PHOTON, YOSEMITE, and RHINE (DME); and PULSAR, TENAYA, and LUCERNE (nAMD). Treatment with aflibercept 8 mg was associated with significantly fewer injections compared with faricimab T&E in patients with DME (mean difference −3.62 [95% credible interval −4.22, −3.02]) or nAMD (−1.47 [−1.90, −1.05]). Mean changes from baseline in BCVA (absolute) or CST (absolute and percentage) did not differ significantly between the two treatments.ConclusionThis NMA indicated that aflibercept 8 mg required significantly fewer injections while maintaining similar efficacy over 2 years of treatment compared with faricimab T&E in patients with DME or nAMD.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40123-025-01247-3.

Objective: To evaluate the short-term efficacy of ranibizumab therapy in terms of visual function and retinal thickness in patients with diabetic macular edema (DME) who failed to respond to treatment with repeated bevacizumab injections. Additionally, parameters affecting outcomes after switching were investigated. Materials and Methods: The present study was a multicenter, retrospective study of 70 eyes with DME non-responding to bevacizumab. All patients were initially treated with at least three consecutive injections of bevacizumab then switched to at least one injection of ranibizumab. A monthly follow-up after the first ranibizumab injection to the last injection within six months was monitored. Primary outcomes included mean change in best-corrected visual acuity (BCVA) and central subfield thickness (CSFT) changes from baseline. Exploratory outcomes included parameters affecting prognosis after switching. Results: Seventy eyes with DME were included in the present study. The mean change of BCVA (logMAR) was 0.075±0.375 (95% CI 0.014 to 0.164, p=0.098). The mean change of CSFT was 58.85±110.37 μm (95% CI 32.54 to 85.17, p&lt;0.001). Forty-two percent of patients had BCVA improvement and 75.71% had CSFT improvement after switching to ranibizumab. Factors associated with BCVA and CSFT improvement were baseline BCVA, baseline CSFT, and older than 50 years old. Conclusion: Switching to ranibizumab therapy in DME patients unresponsive to repeated bevacizumab injection provides better anatomical outcomes than visual acuity improvement. This will help ophthalmologists better understand the benefits on switching therapy to ranibizumab in terms of visual function and retinal thickness in patients with DME in the real-world setting. Keywords: Diabetes, macular edema; Anti-vascular endothelial growth factor (VEGF); Intravitreal injection; Non-responder; Persistent diabetic macular edema

To assess time to, cumulative incidence of, and functional benefit of achieving sustained ≥2-step Diabetic Retinopathy Severity Scale (DRSS) improvement in diabetic macular oedema (DMO). Post hoc analysis of VISTA/VIVID including eyes with DMO treated with intravitreal aflibercept injections (IAI), 2 mg q4 weeks (2q4, n = 250) or q8 weeks after 5 monthly doses (2q8, n = 249), or laser control (n = 249). Changes from baseline in best-corrected visual acuity (BCVA) and central subfield thickness (CST) were evaluated in sustained (≥2 consecutive visits) DRSS subgroups (≥1-step worsening, no change, ≥2-step improvement). Time to sustained ≥2-step DRSS improvement was shorter for both the IAI 2q4 and IAI 2q8 groups versus laser (both log-rank p < 0.001). Cumulative incidences of sustained ≥2-step DRSS improvement with IAI 2q4 and IAI 2q8 versus laser were 40.0% and 42.8% versus 15.5% (both p < 0.001) through week 100. Mean differences (95% CI) in BCVA gains from baseline at weeks 52 and 100 between eyes with sustained ≥2-step DRSS improvement versus sustained ≥1-step DRSS worsening were -3.0 (-8.9, 2.9) and 6.2 (0.2, 12.2) letters with laser, and 4.2 (0.8, 7.6) and 4.9 (1.3, 8.4) letters with IAI combined, respectively. Difference (95% CI) in CST reduction was significantly greater only with IAI combined at week 100 (-83.0 [-140.8, -25.3]). Correlations between BCVA and CST changes were weak. DMO eyes treated with IAI achieved sustained ≥2-step DRSS improvement significantly earlier and more frequently versus laser. This improvement was associated with greater BCVA gains, independent of CST reductions. ClinicalTrials.gov ( https://clinicaltrials.gov/ ) identifiers: NCT01363440 and NCT01331681 .