Neovascular Age-Related Macular Degeneration (nAMD): A Review of Emerging Treatment Options

Figures & data

Table 1 Summary of the Major Anti-VEGF Studies

Study Name (Year Published)	Treatment Arms	Main Outcomes	Safety Profile
MARINA (2006) Number of subjects = 716	- Placebo - Monthly Ranibizumab 0.3mg - Monthly Ranibizumab 0.5mg	At 2 years 1. Both treatment groups were superior to placebo in maintaining vision (loss of < 15 letters) (p<0.001 for both comparisons)  ● 94.5% of Ranibizumab 0.3mg group  ● 94.6% of Ranibizumab 0.5mg group  ● 62.2% of placebo group 2. Both treatment groups were superior in improving vision (gain in ≥ 15 letters) (p<0.001 for both comparisons)  ● 24.8% of Ranibizumab 0.3mg group  ● 33.8% of Ranibizumab 0.5mg group  ● 5% of controls 3. Average change in VA  ● Treated groups: 7 letters gained  ● Controls: 10 letters lost	Endophthalmitis (0 to 1.3%), Uveitis (0 to 1.3%)
ANCHOR (2006) Number of subjects = 423	- Ranibizumab 0.3mg - Ranibizumab 0.5mg - PDT	At 1 year 1. Ranibizumab was superior to PDT in preventing visual loss (MLV ≤ 15 letters) (p<0.001 for each comparison)  ● 94.3% of Ranibizumab 0.3mg group  ● 96.4% of Ranibizumab 0.5mg group  ● 64.3% of PDT group 2. Patients in the Ranibizumab treatment arms had significantly higher gain in visual acuity compared to the PDT group (gain > 15 letters) (p<0.001 for each comparison)  ● 35.7% of Ranibizumab 0.3mg group  ● 40.3% of Ranibizumab 0.5mg group  ● 5.6% of PDT group 3. Patients in the PDT groups had significantly higher rates of severe visual loss (decrease ≥ 30 letters) (p<0.001 for each comparison)  ● 0% of Ranibizumab groups  ● 13% of PDT group	Endophthalmitis (0 to 1.4%), Uveitis (0 to 0.7%)
CATT (2011) Number of subjects = 1208	- Ranibizumab 0.5mg monthly - Ranibizumab 0.5mg PRN - Bevacizumab 1.25mg monthly - Bevacizumab 1.25mg PRN	At 1 year 1. Bevacizumab was non-inferior (limit of ± 5 letters) to Ranibizumab on BCVA improvement when matched for regime  ● + 8.5 letters in Ranibizumab 0.5mg monthly group  ● + 8.0 letters in Bevacizumab 1.25mg group  ● + 6.8 letters in the Ranibizumab 0.5mg PRN group  ● + 5.9 letters in the Bevacizumab 1.25mg PRN group 2. Bevacizumab was non-inferior to Ranibizumab in the prevention of MVL (≥ 15 letters) (p=0.29)  ● 94.4% in Ranibizumab 0.5mg monthly group  ● 94.0% in Bevacizumab 1.25mg monthly group  ● 95.4% in Ranibizumab 0.5mg PRN group  ● 91.5% in Bevacizumab 1.25mg PRN group	Death from any cause (1.3 to 3.7%), Arteriothrombotic event (2.0 to 2.7%), Endophthalmitis (0 to 1.4%)
IVAN (2013) Number of subjects = 525	- Ranibizumab 0.5mg monthly - Ranibizumab 0.5mg PRN - Bevacizumab 1.25mg monthly - Bevacizumab 1.25mg PRN	At 2 years 1. Bevacizumab was non-inferior (limit of ± 3.5 letters) to ranibizumab. Mean difference of −1.37 letters (p=0.26)  ● 67.8 letters in combined Ranibizumab group  ● 66.1 letters in combined Bevacizumab group 2. Discontinuous treatment was non-inferior to continuous treatment. Mean difference of −1.63 letters (p=0.18)  ● 67.3 letters in discontinuous regimen  ● 66.6 letters in continuous regimen	Death from any cause (3 to 7%), Arteriothrombotic event or heart failure (4 to 7%), Venous thrombotic event (1%), Ocular event in study eye (2 to 3%)
VIEW 1 and VIEW 2 (2012) Number of subjects = 2419	- Aflibercept 0.5mg monthly - Aflibercept 2mg monthly - Aflibercept 2mg 2-monthly - Ranibizumab 0.5mg monthly	At 52 weeks 1. All aflibercept groups were non-inferior (limit of ±10%) to ranibizumab in maintaining vision at 52 weeks VIEW 1:  ● 95.1% in Aflibercept 2mg monthly group  ● 95.9% in Aflibercept 0.5mg monthly group  ● 95.1% in Aflibercept 2mg 2-monthly group  ● 94.4% in Ranibizumab 0.5mg monthly group VIEW 2:  ● 95.6% in Aflibercept 2mg monthly group  ● 96.3% in Aflibercept 0.5mg monthly group  ● 95.6% in Aflibercept 2mg 2-monthly group  ● 94.4% in Ranibizumab 0.5mg monthly group 2. [View 1] Only the Aflibercept 2mg monthly group was statistically superior to the Ranibizumab monthly group (p=0.005)  ● + 10.9 letters in Aflibercept 2mg monthly group  ● + 8.1 letters in Ranibizumab 0.5mg monthly group	Endophthalmitis (0 to 1%), Arteriothrombolic event (0.7 to 2.6%)
HAWK (2020) Number of subjects = 1775	- Brolucizumab 3mg 12-weekly (after 3 monthly injections) - Brolucizumab 6mg 12-weekly (after 3 monthly injections) - Aflibercept 2mg 8-weekly	At 48 weeks Brolucizumab was non-inferior to Aflibercept in mean BCVA change from baseline (P<0.01). Least squares mean BCVA change (ETDRS letters):  ● Brolucizumab 3mg: +6.1  ● Brolucizumab 6mg: +6.6  ● Aflibercept 2mg: +6.8 At 96 weeks Brolucizumab was similarly non-inferior to Aflibercept in mean BCVA change from baseline (P<0.01). Least squares mean BCVA change (ETDRS letters):  ● Brolucizumab 3mg: +5.6  ● Brolucizumab 6mg: +5.9  ● Aflibercept 2mg: +5.3	Pooled analysis of data from HAWK and HARRIER reported overall comparable incidences of ocular and non-ocular AEs between Brolucizumab and Aflibercept over 96 weeks. However, intraocular inflammation (iritis and uveitis) was seen at a higher rate with Brolucizumab 6mg vs Aflibercept at week 96 in HAWK (4.7% vs 0.6%) and HARRIER (0.8% vs 0.3%). There were also 10 cases of retinal artery occlusion in the Brolucizumab arms across HAWK and HARRIER.
HARRIER (2021) Number of subjects = 1048	- Brolucizumab 6mg 12-weekly (after 3 monthly injections) - Aflibercept 2mg 8-weekly	At 48 weeks Brolucizumab was non-inferior to Aflibercept in mean BCVA change from baseline (P<0.01). Least squares mean BCVA change (ETDRS letters):  ● Brolucizumab 6mg: +6.6  ● Aflibercept 2mg: +6.8 At 96 weeks Brolucizumab was similarly non-inferior to Aflibercept in mean BCVA change from baseline (P<0.01). Least squares mean BCVA change (ETDRS letters):  ● Brolucizumab 6mg: +6.1  ● Aflibercept 2mg: +6.6
TENAYA (2021) Number of subjects = 671	- Faricimab 6.0mg up to every 16 weeks - Aflibercept 2.0mg every 8 weeks	1. Faricimab group was non-inferior to the aflibercept group in change of BCVA from baseline  ● Faricimab group gained 5.8 letters (95% CI 4.6 to 7.1) compared to 5.1 letters (95% CI 3.9 to 6.4) in the aflibercept group  ● Treatment difference of 0.7 letters (95% CI −1.1 to 2.5)	For both TENAYA and LUCERNE: Intraocular inflammation (1.2 to 2.0%). No cases of retinal vasculitis or occlusive retinitis were reported
LUCERNE (2021) Number of subjects = 658	- Faricimab 6.0mg up to every 16 weeks - Aflibercept 2.0mg every 8 weeks	1. Faricimab group was non-inferior to the aflibercept group in change of BCVA from baseline  ● Faricimab group gained 6.6 letters (95% CI 5.3 to 7.8) compared to 6.6 letters (95% CI 3.9 to 6.4) in the aflibercept group  ● Treatment difference of 0.0 letters (95% CI −1.7 to 1.8)	For both TENAYA and LUCERNE: Intraocular inflammation were 2.0% and 1.2% for faricimab and aflibercept respectively. No cases of retinal vasculitis or occlusive retinitis were reported

Abbreviations: MARINA, Minimally classic/occult trial of the Anti-VEGF antibody Ranibizumab in the treatment of Neovascular AMD; ANCHOR, Anti-VEGF antibody for the treatment of predominantly Classic Choroidal Neovascularisation in AMD; CATT, Comparison of AMD Treatments Trial; IVAN, Inhibit VEGF in Age related CNV; VIEW, VEGF Trap-Eye: Investigation of Efficacy and Safety in Wet AMD; BCVA, Best corrected visual acuity; MLV, Mean loss of vision.