Abstract/Text: AIM: This study aims to assess the impact of continued ranibizumab treatment for neovascular age-related macular degeneration on patients from the MARINA and ANCHOR randomised clinical studies who lost ≥ 3 lines of best-corrected visual acuity (BCVA) at any time during the first year of treatment.
METHODS: Baseline characteristics, mean BCVA over time and ocular adverse events (AEs) were evaluated both for patients whose BCVA loss occurred at any post-baseline visit and for patients whose BCVA loss was acute. The visit when the ≥ 3-line BCVA loss was detected was defined as the new baseline.
RESULTS: Continued monthly ranibizumab treatment led to an improvement in mean BCVA from the new baseline. On average, patients with acute BCVA loss gained 11.9 letters at 3 months after the new baseline, compared with 0.3 letters gained with sham. No strong signals were detected in patient demographics and baseline characteristics for prognostic markers of BCVA loss. Furthermore, there was no pattern in the AE profile of patients with acute BCVA loss to suggest that BCVA recovery could be attributed to spontaneously resolving AEs.
CONCLUSION: Continued ranibizumab treatment appears to be beneficial for patients with neovascular age-related macular degeneration who experience a ≥ 3-line BCVA loss during the first year of treatment.

Abstract/Text: AIM: This study aims to assess the impact of continued ranibizumab treatment for neovascular age-related macular degeneration on patients from the MARINA and ANCHOR randomised clinical studies who lost ≥ 3 lines of best-corrected visual acuity (BCVA) at any time during the first year of treatment.
METHODS: Baseline characteristics, mean BCVA over time and ocular adverse events (AEs) were evaluated both for patients whose BCVA loss occurred at any post-baseline visit and for patients whose BCVA loss was acute. The visit when the ≥ 3-line BCVA loss was detected was defined as the new baseline.
RESULTS: Continued monthly ranibizumab treatment led to an improvement in mean BCVA from the new baseline. On average, patients with acute BCVA loss gained 11.9 letters at 3 months after the new baseline, compared with 0.3 letters gained with sham. No strong signals were detected in patient demographics and baseline characteristics for prognostic markers of BCVA loss. Furthermore, there was no pattern in the AE profile of patients with acute BCVA loss to suggest that BCVA recovery could be attributed to spontaneously resolving AEs.
CONCLUSION: Continued ranibizumab treatment appears to be beneficial for patients with neovascular age-related macular degeneration who experience a ≥ 3-line BCVA loss during the first year of treatment.

Abstract/Text: PURPOSE: To determine efficacy and safety of intravitreal aflibercept in patients with neovascular age-related macular degeneration (AMD) during a second year of variable dosing after a first-year fixed-dosing period.
DESIGN: Two randomized, double-masked, active-controlled, phase 3 trials.
PARTICIPANTS: Two thousand four hundred fifty-seven patients with neovascular AMD.
METHODS: From baseline to week 52, patients received 0.5 mg intravitreal ranibizumab every 4 weeks (Rq4), 2 mg aflibercept every 4 weeks (2q4), 0.5 mg aflibercept every 4 weeks (0.5q4), or 2 mg aflibercept every 8 weeks (2q8) after 3 monthly injections. During weeks 52 through 96, patients received their original dosing assignment using an as-needed regimen with defined retreatment criteria and mandatory dosing at least every 12 weeks.
MAIN OUTCOME MEASURES: Proportion of eyes at week 96 that maintained best-corrected visual acuity (BCVA; lost <15 letters from baseline); change from baseline in BCVA.
RESULTS: Proportions of eyes maintaining BCVA across treatments were 94.4% to 96.1% at week 52 and 91.5% to 92.4% at week 96. Mean BCVA gains were 8.3 to 9.3 letters at week 52 and 6.6 to 7.9 letters at week 96. Proportions of eyes without retinal fluid decreased from week 52 (60.3% to 72.4%) to week 96 (44.6% to 54.4%), and more 2q4 eyes were without fluid at weeks 52 and 96 than Rq4 eyes (difference of 10.4% [95% confidence interval {CI}, 4.9-15.9] and 9.0% [95% CI, 3.0-15.1]). Patients received on average 16.5, 16.0, 16.2, and 11.2 injections over 96 weeks and 4.7, 4.1, 4.6, and 4.2 injections during weeks 52 through 96 in the Rq4, 2q4, 0.5q4, and 2q8 groups, respectively. The number of injections during weeks 52 through 96 was lower in the 2q4 and 2q8 groups versus the Rq4 group (differences of -0.64 [95% CI, -0.89 to -0.40] and -0.55 [95% CI, -0.79 to -0.30]; P < 0.0001, post hoc analysis). Incidences of Antiplatelet Trialists' Collaboration-defined arterial thromboembolic events were similar across groups (2.4% to 3.8%) from baseline to week 96.
CONCLUSIONS: All aflibercept and ranibizumab groups were equally effective in improving BCVA and preventing BCVA loss at 96 weeks. The 2q8 aflibercept group was similar to ranibizumab in visual acuity outcomes during 96 weeks, but with an average of 5 fewer injections. Small losses at 96 weeks in the visual and anatomic gains seen at 52 weeks in all arms were in the range of losses commonly observed with variable dosing.

Copyright © 2014 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Abstract/Text: PURPOSE: We sought to evaluate longer-term efficacy and safety of intravitreal aflibercept monotherapy (IAI) vs IAI plus rescue photodynamic therapy (rPDT) in patients with polypoidal choroidal vasculopathy (PCV).
DESIGN: This was a prospective multicenter, double-masked, sham-controlled randomized clinical study across 62 centers.
METHODS: In this phase 3b/4 study, patients with PCV with best-corrected visual acuity of 73-24 Early Treatment Diabetic Retinopathy Study letters (20/40-20/320 Snellen equivalent) received IAI 2 mg every 4 weeks until week 12, when they were randomized 1:1 to receive IAI or IAI plus rPDT if rescue criteria were met. Patients not requiring rescue received IAI every 8 weeks; those requiring rescue received IAI every 4 weeks plus sham/active PDT. At week 52 (the primary endpoint), IAI was noninferior to IAI plus rPDT. After week 52, treatment intervals could be extended beyond 8 weeks at the investigators' discretion. Noninferiority of IAI vs IAI plus rPDT for mean best-corrected visual acuity change from baseline to week 96 was evaluated.
RESULTS: Over 96 weeks, 54 patients (17.0%) met rescue criteria. At week 96, IAI was noninferior to IAI plus rPDT in terms of Early Treatment Diabetic Retinopathy Study letters gained (+10.7 vs +9.1, P = .48). Proportions of patients with complete polyp regression (33.1% vs 29.1%) or without active polyps (82.1% vs 85.6%) were similar. In year 2, the mean number of injections was 4.6 in both arms. No new safety signals were observed.
CONCLUSION: IAI monotherapy was noninferior to IAI with rescue PDT up to 96 weeks, and functional and anatomical improvements achieved at 52 weeks were maintained. Few patients required rescue PDT, which provided no additional visual benefit.

Copyright © 2019. Published by Elsevier Inc.

Abstract/Text: PURPOSE: To report the 96-week outcomes from HAWK and HARRIER.
DESIGN: Phase 3, prospective, randomized, double-masked, multicenter studies comparing efficacy and safety of brolucizumab 3 mg (HAWK only) and 6 mg with aflibercept 2 mg in eyes with neovascular age-related macular degeneration (nAMD).
PARTICIPANTS: Treatment-naïve eyes with nAMD were randomized 1:1:1 to brolucizumab 3 mg (n = 358), brolucizumab 6 mg (n = 360), aflibercept 2 mg (n = 360; HAWK) or 1:1 to brolucizumab 6 mg (n = 370), aflibercept 2 mg (n = 369; HARRIER).
METHODS: After 3 monthly loading doses, brolucizumab patients received every (q)-12-week (w) dosing, possibly adjusting to q8w dosing if disease activity was present at predefined disease activity assessment (DAA) visits. Aflibercept was dosed in a fixed q8w regimen. Visual and anatomic parameters were assessed throughout. Primary end point was at week 48 (48w), confirmed at 96w.
MAIN OUTCOME MEASURES: Mean best-corrected visual acuity (BCVA) change from baseline, proportion of patients on an q12w regimen, retinal thickness, retinal fluid changes, and safety, all to 96w.
RESULTS: Mean change (least squares [LS] mean ± standard error) in BCVA from baseline to 96w in HAWK was 5.6±0.79 Early Treatment Diabetic Retinopathy Study (ETDRS) letters for brolucizumab 3 mg, 5.90±0.78 letters for brolucizumab 6 mg, and 5.3±0.78 letters for aflibercept and in HARRIER was 6.1±0.73 letters for brolucizumab 6 mg and 6.6 ± 0.73 letters for aflibercept. Greater central subfield thickness reductions were observed with brolucizumab 6 mg versus aflibercept in HAWK (LS mean, -174.8 μm vs. -148.7 μm; 95% confidence interval for treatment difference, -46.2 to -5.9 μm; P = 0.0115) and HARRIER (LS mean, -197.7 μm vs. -155.1 μm; 95% confidence interval for treatment difference, -62.0 to -23.3 μm; P < 0.0001). The proportions of eyes with intraretinal fluid and/or subretinal fluid (IRF/SRF) at 96w in HAWK were 31% (P = 0.0688) and 24% (P = 0.0002) for brolucizumab 3 mg and 6 mg and 37% for aflibercept, whereas in HARRIER, they were 24% for brolucizumab 6 mg (P < 0.0001) and 39% for aflibercept. At 92w (last DAA), a 45.4% and 38.6% probability was observed for brolucizumab 6 mg patients of maintaining an q12w treatment regimen in HAWK and HARRIER, respectively. Brolucizumab exhibited an overall well-tolerated safety profile.
CONCLUSIONS: Visual outcomes from 48w to 96w confirm the efficacy achieved at 48w. Brolucizumab demonstrated greater fluid resolution compared with aflibercept. The q12w potential for brolucizumab observed at 48w was maintained to 96w.

Copyright © 2020 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Abstract/Text: BACKGROUND: Faricimab is a bispecific antibody that acts through dual inhibition of both angiopoietin-2 and vascular endothelial growth factor A. We report primary results of two phase 3 trials evaluating intravitreal faricimab with extension up to every 16 weeks for neovascular age-related macular degeneration (nAMD).
METHODS: TENAYA and LUCERNE were randomised, double-masked, non-inferiority trials across 271 sites worldwide. Treatment-naive patients with nAMD aged 50 years or older were randomly assigned (1:1) to intravitreal faricimab 6·0 mg up to every 16 weeks, based on protocol-defined disease activity assessments at weeks 20 and 24, or aflibercept 2·0 mg every 8 weeks. Randomisation was performed through an interactive voice or web-based response system using a stratified permuted block randomisation method. Patients, investigators, those assessing outcomes, and the funder were masked to group assignments. The primary endpoint was mean change in best-corrected visual acuity (BCVA) from baseline averaged over weeks 40, 44, and 48 (prespecified non-inferiority margin of four letters), in the intention-to-treat population. Safety analyses included patients who received at least one dose of study treatment. These trials are registered with ClinicalTrials.gov (TENAYA NCT03823287 and LUCERNE NCT03823300).
FINDINGS: Across the two trials, 1329 patients were randomly assigned between Feb 19 and Nov 19, 2019 (TENAYA n=334 faricimab and n=337 aflibercept), and between March 11 and Nov 1, 2019 (LUCERNE n=331 faricimab and n=327 aflibercept). BCVA change from baseline with faricimab was non-inferior to aflibercept in both TENAYA (adjusted mean change 5·8 letters [95% CI 4·6 to 7·1] and 5·1 letters [3·9 to 6·4]; treatment difference 0·7 letters [-1·1 to 2·5]) and LUCERNE (6·6 letters [5·3 to 7·8] and 6·6 letters [5·3 to 7·8]; treatment difference 0·0 letters [-1·7 to 1·8]). Rates of ocular adverse events were comparable between faricimab and aflibercept (TENAYA n=121 [36·3%] vs n=128 [38·1%], and LUCERNE n=133 [40·2%] vs n=118 [36·2%]).
INTERPRETATION: Visual benefits with faricimab given at up to 16-week intervals demonstrates its potential to meaningfully extend the time between treatments with sustained efficacy, thereby reducing treatment burden in patients with nAMD.
FUNDING: F Hoffmann-La Roche.

Copyright © 2022 Elsevier Ltd. All rights reserved.