Comparability of aflibercept biosimilar with reference aflibercept in diabetic macular edema: subgroup analysis of the pivotal Phase-III INSIGHT randomized clinical trial

Biosimilars may be lower-cost alternatives to originator biologic products, potentially offering expanded access or reduced economic burden, but have not been evaluated with aflibercept in diabetic macular edema (DME). To compare efficacy and safety of MYL-1701P, an aflibercept biosimilar, with reference aflibercept (Eylea [Regeneron]) in DME. This was a double-masked, randomized clinical trial that included participants at 77 centers across the US, Europe, Japan, and India. Included in the analysis were individuals 18 years and older with type 1 or type 2 diabetes with central DME and best-corrected visual acuity (BCVA) letter score of 73 to 38 in the study eye using an Early Treatment Diabetic Retinopathy Study (ETDRS) chart. Study data were analyzed from October to December 2021. Formulations of MYL-1701P (0.5-mg vial) or reference aflibercept every 4 weeks for 5 consecutive intravitreal injections, followed by every 8 weeks through week 52. The primary outcome was the adjusted difference in least squares mean (SE) change from baseline BCVA letter score at week 8 with an equivalence margin of -3 to +3 letters. Secondary outcomes included change in central subfield thickness (CST), BCVA, number of injections over 52 weeks, incidence of adverse events (AEs), and antidrug antibodies (ADAs). A total of 355 participants (mean [SD] age, 62.2 [9.2] years; 216 male [60.8%]) were randomized to MYL-1701P (179 participants [50.4%]) and aflibercept (176 participants [49.6%]). At week 8, mean (SE) change in BCVA was 6.60 (0.55) letters vs 6.56 (0.55) letters in the MYL-1701P vs aflibercept groups. The adjusted mean difference of 0.04 letters (90% CI, -1.16 to 1.24 letters) met the primary outcome. At week 8, mean (SE) change in CST was -112 (7) μm vs -124 (7) μm in the MYL-1701P vs aflibercept groups (adjusted mean difference, 12 μm; 90% CI, -3 to 26 μm). The incidence of treatment-emergent AEs in the MYL-1701P and aflibercept arms were ocular (30.9% [55 of 178] vs 29.5% [52 of 176]), serious ocular (0.6% [1 of 178] vs 1.1% [2 of 176]), nonocular (65.2% [116 of 178] vs 65.3% [115 of 176]), and serious nonocular (16.9% [30 of 178] vs 11.9% [21 of 176]). The mean (SD) total number of injections was 8.4 (2.1) vs 8.7 (1.8) in the MYL-1701P vs aflibercept groups. The incidence of treatment-induced or treatment-boosted ADAs was 2.8% (5 of 177) vs 5.7% (10 of 176) in the MYL-1701P vs aflibercept arms. MYL-1701P demonstrated clinical equivalence in regard to efficacy, with comparable safety and immunogenicity, to reference aflibercept. These findings support use of MLY-1701P as an alternative to reference aflibercept. ClinicalTrials.gov Identifier: NCT03610646.

To assess the effect of intravitreal bevacizumab on diabetic macular oedema (DMO) and retinal vessel calibres. We performed a consecutive case series study in which 10 consecutive eyes with diffuse DMO, two of which had not previously been treated, received an intravitreal injection of bevacizumab 1 mg, which was followed by two more injections at 6-week intervals. Fundus photography and optical coherence tomography (OCT) were carried out at baseline immediately before injection and at 1, 2.5 and 4 months after the first injection. Outcome measures were best corrected visual acuity (BCVA) in Early Treatment Diabetic Retinopathy Study letters, macular volume, foveal subfield thickness and vessel diameter measurement. Intravitreal administration of bevacizumab was followed by a mean increase in BCVA of 7.3 +/- 17 (mean +/- standard deviation) letters between baseline and month 4, which was 1 month after the last injection (p < 0.0001). This was accompanied by a reduction in mean macular volume from 9.90 +/- 1.9 mm(3) to 8.96 +/- 2.4 mm(3) (p = 0.002) and in foveal subfield thickness from 447 +/- 117 microm to 388 +/- 117 microm (p = 0.03). Two eyes with early proliferative diabetic retinopathy lost all signs of proliferation without any evidence of fibrosis. Although there was a trend towards vasoconstriction, the changes in vessel diameters (arteries and veins) after 4 months of intravitreal Avastin injection were not statistically significant (p = 0.9 and p = 0.17, respectively). Foveal thickness in non-injected fellow eyes with DMO changed from 428 +/- 153 microm at baseline to 383 +/- 151 microm at 4 months (p = 0.1), which did not reach statistical significance. Intravitreal bevacizumab 1 mg every 6 weeks was followed by a moderate reduction in DMO without normalization of foveal and macular thickness. Our observations suggest that a larger study where patients are examined sooner after injection is needed to elucidate the potential relationship between changes in retinal vessel diameters and thickness changes in DMO.

Association of the Charlson Comorbidity Index with one-year outcomes in patients with macular edema secondary to retinal vein occlusion.

Efficacy and Safety of Suprachoroidal CLS-TA for Macular Edema Secondary to Noninfectious Uveitis: Phase 3 Randomized Trial

Results of this review document the comparative effectiveness of aflibercept versus ranibizumab for visual acuity and morphological outcomes in eyes with neovascular AMD. Current available information on adverse effects of each medication suggests that the safety profile of aflibercept is comparable with that of ranibizumab; however, the number of participants who experienced adverse events was small, leading to imprecise estimates of absolute and relative effect sizes. The eight-week dosing regimen of aflibercept represents reduced treatment requirements in comparison with monthly dosing regimens and thus has the potential to reduce treatment burden and risks associated with frequent injections.

BackgroundThis post hoc analysis compared the efficacy and safety of suprachoroidally administered triamcinolone acetonide (CLS‐TA) to other commonly available treatments for non‐infectious uveitis.MethodsResults from the PEACHTREE study were compared between subjects randomised to CLS‐TA not requiring rescue therapy and those subjects randomised to control, who subsequently required rescue therapy. Endpoints included best corrected visual acuity (BCVA), central subfield thickness (CST), treatment emergent adverse events and intraocular pressure (IOP) related safety findings.ResultsIn this analysis, there were 83 unrescued CLS‐TA subjects and 46 rescued control subjects. At Week 24, 51.9% of the unrescued CLS‐TA subjects gained ≥15 letters in BCVA, compared to 37.0% of the rescued control subjects (p = 0.115). Unrescued CLS‐TA subjects showed a mean gain of 15.7 versus 10.9 letters in rescued control subjects (p = 0.080). A significantly greater mean reduction in CST was observed for unrescued CLS‐TA subjects versus rescued control subjects (174.0 and 148.5 μm; p = 0.040). Of unrescued CLS‐TA subjects, 4.9% experienced IOP elevations ≥30 mm Hg at any visit versus 10.9% of rescued control subjects. Further, use of IOP‐lowering medications appeared lower in unrescued CLS‐TA subjects versus rescued control subjects (7.2% vs. 13.0%). There were no IOP‐lowering surgical interventions in either group.ConclusionCLS‐TA subjects experienced significantly greater reduction in CST and tended towards greater improvement in BCVA, compared with rescued control subjects. Suprachoroidally administered CLS‐TA showed a lower incidence of IOP‐related safety findings.

Purpose: The purpose of this article is to compare the fellow-eye effect of unilateral intravitreal antivascular endothelial growth factor (anti-VEGF) treatment (bevacizumab, ranibizumab, and aflibercept) in patients with bilateral diabetic macular edema (DME). Methods: A retrospective review was conducted of hemoglobin A1c-matched groups receiving unilateral anti-VEGF injections (1.25 mg bevacizumab, 0.5 mg ranibizumab, and 2 mg aflibercept) in which the second eye had subclinical DME. Two main outcome measures evaluated were central subfield thickness (CST) on optical coherence tomography and best-corrected visual acuity (BCVA). Patients were excluded if they had poor BCVA (&lt; 20/100) or had received laser, vitrectomy, filtering surgery, or pharmacologic treatments in the 3 months prior in the noninjected eye. Results: A total of 2073 total intravitreal anti-VEGF injections for DME were reviewed and 94 met the inclusion criteria: 40 bevacizumab, 33 ranibizumab, and 21 aflibercept. At 1 month, the CST of the fellow eye in the bevacizumab group had a statistically significant decrease (296.82 µm to 292.46 µm, P = .01) while both the ranibizumab and aflibercept groups trended toward worsening edema. When compared to ranibizumab and aflibercept, the CST in the noninjected eye in the bevacizumab group had improvements of –15.03 µm and –13.47 µm, respectively ( P &lt; .019). When bevacizumab was switched to ranibizumab or aflibercept, the edema in the fellow eye worsened by +49.60 µm and +5.50 µm, respectively. Conclusion: Bevacizumab injection has a statistically significant therapeutic effect in the fellow eye when compared to those treated with ranibizumab and aflibercept. The edema in the fellow eye worsened when injection in the primary eye was switched away from bevacizumab.

Adding a laser-induced chorioretinal anastomosis (L-CRA) to current treatments for central retinal vein occlusion (CRVO) may improve outcomes and lessen therapy burdens. To determine the 2-year efficacy of intravitreal ranibizumab with an L-CRA vs ranibizumab alone for patients with macular edema caused by CRVO. In this randomized clinical trial conducted at a single university clinic from March 2012 to June 2015, 58 participants with macular edema caused by CRVO were randomized 1:1 to either an L-CRA or sham procedure at baseline. All participants received monthly intravitreal injections of ranibizumab, 0.5 mg. Data were analyzed from April 2017 to September 2017. Random assignment to L-CRA plus monthly injections of intravitreal ranibizumab, 0.5 mg, (combination group; n = 29) or to a sham L-CRA procedure plus monthly injections of intravitreal ranibizumab, 0.5 mg, (ranibizumab alone group; n = 29) for 6 months. From month 7 to month 24, participants were evaluated monthly and received an injection of ranibizumab if a loss of 5 or more letters of best-corrected visual acuity (BCVA) on ETDRS chart from previous highest score occurred or if there was evidence of residual macular edema on optical coherence tomography. Mean number of injections from month 7 to month 24, change in BCVA, and change in central subfield thickness (CST). Of the 58 included participants, 38 (66%) were men, and the mean (SD) age was 68.6 (11.8) years; participants had a mean (SD) BCVA of 57.09 (11.87) ETDRS letters (Snellen equivalent, 20/73) and a mean (SD) CST of 738.36 (175.54) μm. A successful L-CRA was created in 24 of 29 participants (83%) in the combination group. The mean number of injections from month 7 to month 24 was 3.2 (95% CI, 2.5-3.8) in the combination group and 7.1 (95% CI, 6.0-8.0) in the ranibizumab alone group. The ratio of the number of injections in the combination group compared with the ranibizumab alone group was 0.46 (95% CI, 0.36-0.61; P < .001). Mixed-effects regression modeling showed a difference in mean BCVA at 2 years between the combination and ranibizumab alone groups (combination, 70.3 letters [Snellen equivalent, 20/40]; ranibizumab alone, 61.6 letters [Snellen equivalent, 20/60]; difference, 8.8 letters; 95% CI, 0.2-17.3; P = .05). There was also a difference in CST at 2 years between the combination and ranibizumab alone groups (mean CST: combination, 303.6 μm; ranibizumab alone, 394.5 μm; difference, 90.9 μm; 95% CI, 24.3-157.5; P = .01). Four participants (14%) in the combination group required a vitrectomy for early macular traction or vitreous hemorrhage. For macular edema caused by CRVO, an L-CRA significantly reduced the number of ranibizumab injections required. anzctr.org.au Identifier: ACTRN12612000004864.

Enhanced Benefit in Diabetic Macular Edema from AKB-9778 Tie2 Activation Combined with Vascular Endothelial Growth Factor Suppression

PurposeThis meta-analysis aims to summarize 12-month best-corrected visual acuity (BCVA) outcomes in response to anti-vascular endothelial growth factor (VEGF) therapy and dexamethasone implant for the treatment of diabetic macular edema (DME) and to identify factors affecting treatment response using evidence generated from meta-regression.MethodsA systematic review of electronic databases was conducted to identify randomized controlled trials (RCTs) and real-life/observational studies that reported 12-month changes in BCVA in patients with DME on anti-VEGF or dexamethasone implant treatment in monotherapy. Study factors that were analyzed are baseline patient characteristics, study type, drug employed, number of injections and 12-month change in BCVA. Data were pooled in a random-effects meta-analysis with BCVA change as the main outcome. Meta-regression was conducted to assess the impact of multiple covariates.ResultsOne-hundred-five heterogeneous study populations (45,032 eyes) were identified and included in the analysis. The use of anti-VEGFs and dexamethasone implant induced an overall increase of +8.13 ETDRS letters in BCVA at 12 months of follow-up. Meta-regression provided evidence that mean BCVA change using anti-VEGFs was not statistically higher for RCTs (p=0.35) compared to observational studies. Dexamethasone implant showed a trend for better results in observational studies over RCTs. Populations following a fixed aflibercept regimen performed better than those following a reactive treatment regimen. Mean BCVA gain was higher in younger populations (p<0.001), with lower baseline BCVA (p<0.0001) and longer diabetes duration (p<0.0001), receiving a higher number of injections (p<0.0001).ConclusionIntravitreal therapy with anti-VEGFs or dexamethasone implant produces a significant improvement in BCVA at 12 months in patients with DME. Meta-regression identified the modifiable covariates that can be targeted in order to maximize functional results.

Purpose: To report the 5-year outcomes of intravitreal aflibercept in patients with macular edema due to central retinal vein occlusion (CRVO). Methods: Participants in this study were 51 treatment-naïve patients with macular edema due to CRVO, who received intravitreal aflibercept 2.0 mg using a treat-and-extend regimen after a loading dose of three-monthly injections. The primary outcomes were the mean change in best-corrected visual acuity (BCVA) and central subfield thickness (CST) at month 60 compared with baseline. Results: At month 60, there was a statistically significant improvement in BCVA with a mean change of 11.5 letters compared with baseline (P &lt; 0.001). A total of 19.6% of patients gained ≥15 ETDRS letters compared with baseline. Accordingly, at month 60, there was a statistically significant reduction in CST of approximately 195 µm compared with baseline (P &lt; 0.001). The mean number of injections at month 60 was 23.7. At month 60, approximately 50% of patients were found to have “good” treatment response, which was associated with ellipsoid zone integrity and the absence of hyperreflective foci on optical coherence tomography. It is worthy to note that 60.8% of patients achieved treatment interval of ≥8 weeks, while 31.4% of patients ≥12 weeks. Factors associated with an extended treatment interval were intact ellipsoid zone, lower baseline CST, and the absence of disorganization of inner retinal layers. Conclusion: At the 5-year follow-up, intravitreal aflibercept showed a mean gain of 11.5 letters in BCVA with an average of 23.7 injections. A total of 31.4% of patients achieved a treatment interval of ≥12 weeks, while about half of patients showed good treatment response.

Evaluation of the siRNA PF-04523655 versus Ranibizumab for the Treatment of Neovascular Age-related Macular Degeneration (MONET Study)

PurposeTo evaluate the correlations between swept-source optical coherence tomography angiography (SS-OCTA) parameters and clinical outcomes in eyes with neovascular age-related macular degeneration (nAMD) administered a bimonthly intravitreal aflibercept regimen.MethodsThis prospective, single-arm, interventional study enrolled 33 patients with treatment-naïve nAMD. The eyes received three monthly aflibercept injections followed by five bi-monthly regimens (total 50 weeks). The structural parameters including central subfield thickness (CST) and 5 mm pigment epithelial detachment (PED) volume and microvascular parameters including macular neovascularization (MNV) area, vessel density (VD), and vessel length density (VLD) were recorded every before and 1 week after treatment.ResultsPatients who gained > 5 letters of best-corrected visual acuity (BCVA) from the baseline showed greater decreases in VD and VLD during the loading phase. Patients without recurrent or persistent fluid during the maintenance phase showed greater decreases in CST and 5 mm PED volume after the first injection. The decrease in mean VD during the loading phase was significantly correlated with the final BCVA (r = -0.820, p = 0.004). Moreover, the decrease in mean VLD during the loading phase was significantly correlated with the improvement in the final BCVA (r = -0.726, p = 0.017).ConclusionsThe decrease in mean VD during the loading phase was significantly negatively correlated with the final BCVA at the last visit. The decrease in mean VLD during the loading phase, mean CST during the loading phase, and the improvement in final BCVA showed significant correlations. Therefore, early changes in OCTA microvascular and OCT structural parameters could help predict clinical outcomes in nAMD.Trial RegistrationThe trial was registered with the Clinical Research Information Service (CRIS), which joined the WHO International Clinical Trials Registry Platform (ICTRP) (Registration number: KCT0007375, Date of first trial registration: 10/06/2022).

Intravitreal Aflibercept for Treatment-Resistant Neovascular Age-related Macular Degeneration

Faricimab, a monoclonal bispecific antibody, has recently been incorporated into clinical practice in China. This study main to evaluate the efficacy and safety of intravitreal faricimab in patients with previously treated nAMD and DME under real-world clinical conditions, and to investigate potential associations. In this study, patients with nAMD or DME previously treated with other anti-VEGF (Anti-vascular endothelial growth factor) agents or Ozurdex received faricimab. Changes in best-corrected visual acuity (BCVA), central subfield thickness (CST), and central subfield maximum thickness (CSMT) were assessed. For nAMD, choroidal neovascularization cross-sectional area (CSA) was measured. Optical coherence tomography (OCT) biomarkers were analyzed, and their correlation with BCVA was examined using Spearman analysis. At week 16, BCVA improved from 0.92 to 0.76 logMAR in nAMD and from 0.86 to 0.68 logMAR in DME. CST and CSMT significantly decreased from week 4 to 16 (CST: 539.38 to 408.50μm in nAMD, 502.81 to 292.64μm in DME; CSMT: 710.18 to 526.79μm in nAMD, 586.96 to 356.82μm in DME). CSA reduced from 9.06 to 7.26mm². BCVA positively correlated with subretinal fluid in nAMD and with external limiting membrane/ellipsoid zone integrity in DME, but negatively with subretinal hyperreflective material. No serious adverse events occurred. No serious adverse events were observed. In a real-world setting, intravitreal faricimab demonstrated a favorable safety profile and robust anatomical response in treating treatment-experienced nAMD and DME. However, the anatomical response was stronger than the visual gain in these treatment-experienced eyes, which often have limited visual potential. This study was a Retrospective observational study that approved by the Second Affiliated Hospital of Chongqing Medical University(2025IIT904).