Table 1.
Summary of Phase III trials evaluating the efficacy and safety of ranibizumab
| Study | n | Length of study | Study design | Treatment groups | Results |
|---|---|---|---|---|---|
| Neovascular AMD, FDA-approved 2006 | |||||
| MARINA9 | 716 | 2 years | Multicenter, randomized, double-blind, sham-controlled study | 1) Sham injection 2) Ranibizumab 0.3 mg 3) Ranibizumab 0.5 mg |
• 92% of patients treated with ranibizumab 0.3 mg and 90% of patients treated with ranibizumab 0.5 mg lost <15 letters compared to 52.9% of patients receiving sham injection (P<0.001) • 26.1%, 33.3%, and 3.8% of patients in the ranibizumab 0.3 mg and 0.5 mg groups and sham group, respectively, had an increase of ≥15 letters (P<0.001) |
| ANCHOR10,11 | 423 | 2 years | Multicenter, randomized, double-masked, active-treatment-controlled study | 1) PDT and sham injection 2) Ranibizumab 0.3 mg and sham PDT 3) Ranibizumab 0.5 mg and sham PDT |
• 94.3%, 96.4%, and 64.3% of patients in the ranibizumab 0.3 mg and 0.5 mg and PDT, respectively, lost <15 letters (P<0.001) • Improvement in vision ≥15 letters was reported in 35.7% in the ranibizumab 0.3 mg group, 40.3% in the ranibizumab 0.5 mg group, and 5.6% in the PDT group (P<0.001) |
| PIER12,13 | 184 | 2 years | Multicenter, randomized, double-masked, sham-controlled study | 1) Sham injection 2) Ranibizumab 0.3 mg 3) Ranibizumab 0.5 mg Eligible patients in groups 1 and 2 were switched to 0.5 mg after 1 year |
• VA decline from baseline in 21.4, 2.2, and 2.3 letters in the sham and ranibizumab 0.3 mg and 0.5 mg groups, respectively (P<0.0001) • Decline in vision <15 letters was reported in 78.2% of patients in the ranibizumab 0.3 mg group, 82% of patients in the ranibizumab 0.5 mg group, and 41.3% of patients in the sham group (P<0.0001) • There was no significant difference in the percentage of patients gaining ≥15 letters in the sham and ranibizumab 0.3 mg and 0.5 mg groups: 4.8, 15, and 8.2, respectively |
| HORIZON14 | 853 | ≥4 years | Multicenter, open-label, extension study | 1) Ranibizumab-initial 2) Control crossed-over to ranibizumab 3) Ranibizumab untreated |
• The mean change in BCVA from baseline at the time of the initial study was +2 letters and −11.8 letters in the ranibizumab-initial group and pooled control cross-over to ranibizumab and ranibizumab untreated groups • The proportion of patients with ATEs was 5.3% in both ranibizumab-initial and control cross-over to ranibizumab groups and 3.2% in the untreated group (P=0.76) |
| SAILOR15 | 4,300 | 1 year | Multicenter, randomized or open-label study | 1) Cohort 1: ranibizumab 0.3 mg and 2) ranibizumab 0.5 mg 3) Cohort 2: ranibizumab 0.5 mg |
• The rates of key ocular SAEs in cohort 1 were <1%, and the rates of key ocular and nonocular SAEs were similar across all dose groups • Prior stroke and history of arrhythmias and congestive heart failure were risk factors for stroke • In treatment-naïve patients in cohort 1, 14.6% of patients in the ranibizumab 0.3 mg group and 19.3% in the ranibizumab 0.5 mg group gained ≥15 letters • In previously treated patients in cohort 1, 15.8% and 16.5% of patients in the ranibizumab 0.3 mg and 0.5 mg groups, respectively, gained ≥15 letters • The greatest VA and anatomical changes occurred after the 3 monthly loading doses |
| HARBOR16,17 | 1,098 | 2 years | Multicenter, randomized, double-masked, dose response study | 1) Ranibizumab 0.5 mg monthly 2) Ranibizumab 0.5 mg PRN 3) Ranibizumab 2.0 mg monthly 4) Ranibizumab 2.0 mg PRN |
• There was no evidence that ranibizumab 2.0 mg monthly is superior to 0.5 mg monthly • The ranibizumab 0.5 mg and 2.0 mg PRN groups did not meet the 4-letter noninferiority margin compared to ranibizumab 0.5 mg monthly • At 1 year, the mean gain in BCVA from baseline was 9.1, 7.9, 8.0, and 7.6 letters in the ranibizumab 0.5 mg monthly, 0.5 mg PRN, 2.0 mg monthly, and 2.0 mg PRN groups, respectively • The proportion of patients that gained ≥15 letters was 34.5%, 33.1%, 37.6%, and 34.5% in the ranibizumab 0.5 mg monthly, 0.5 mg PRN, 2.0 mg monthly and 2.0 mg PRN groups, respectively |
| RVO, FDA-approved 2010 | |||||
| BRAVO18 | 397 | 6 months | Multicenter, randomized, double-masked, sham-injection controlled study | 1) Sham injection 2) Ranibizumab 0.3 mg 3) Ranibizumab 0.5 mg |
• Patients gained a mean of 16.6 and 18.3 letters in the ranibizumab 0.3 mg and 0.5 mg groups, respectively, compared to 7.3 letters in the sham-injection group (P<0.0001) • Improvement in BCVA was greater for patients diagnosed with BRVO <3 months before the study screening: 6.3, 16.1 and 16.1 letters for sham and ranibizumab 0.3 mg and 0.5 mg, respectively • 28.8%, 55.2% and 61.1% of patients in the sham and ranibizumab 0.3 mg and 0.5 mg groups, respectively, gained ≥15 letters (P<0.0001) • The mean change in CFT was −337.3 μm, −345.2 μm, and −157.7 μm in the ranibizumab 0.3 mg and 0.5 mg and sham groups, respectively (P<0.0001) |
| CRUISE21 | 392 | 6 months | Multicenter, randomized, double-masked, sham-injection controlled study | 1) Sham injection 2) Ranibizumab 0.3 mg 3) Ranibizumab 0.5 mg |
• Patients gained a mean of 12.7 and 14.9 letters in the ranibizumab 0.3 mg and 0.5 mg groups, respectively, compared to 0.8 letters in the sham-injection group (P<0.0001) • Improvement in BCVA in patients diagnosed with CRVO <3 months before the study screening was 13.2 letters in both ranibizumab groups and was 10.5 and 15.3 letters in the ranibizumab 0.3 mg and 0.5 mg groups in patients diagnosed ≥3 months before screening 16.9%, 46.2%, and 47.7% of patients in the sham and ranibizumab 0.3 mg and 0.5 mg groups gained ≥15 letters, respectively (P<0.0001) • The mean change in CFT was −433.7 μm, −52.3 μm, and −167.7 μm in the ranibizumab 0.3 mg and 0.5 mg and sham groups, respectively (P<0.0001) |
| DME, FDA-approved 2012 | |||||
| RISE25 | 377 | 2 years | Multicenter, randomized, double-masked, sham-injection controlled study | 1) Sham injection 2) Ranibizumab 0.3 mg 3) Ranibizumab 0.5 mg |
• 44.8% and 39.2% of patients in the ranibizumab 0.3 mg and 0.5 mg groups gained ≥15 letters compared to 18.1% in the sham group (P<0.0001 and P=0.0002, respectively) • 89.8% of patients in the sham group compared to 97.6% of patients in both the ranibizumab 0.3 mg and 0.5 mg groups lost <15 letters (P=0.0086 and P=0.0126, respectively) • There was a rapid improvement in vision within the first 7 days after treatment initiation in ranibizumab-treated patients • CFT decreased by 133.4 μm, 250.6 μm, and 253.1 μm in the sham and ranibizumab 0.3 mg and 0.5 mg groups, respectively (P<0.0001) |
| RIDE25 | 382 | 2 years | Multicenter, randomized, double-masked, sham-injection controlled study | 1) Sham injection 2) Ranibizumab 0.3 mg 3) Ranibizumab 0.5 mg |
• 33.6% and 45.7% of patients in the ranibizumab 0.3 mg and 0.5 mg groups, respectively, gained ≥15 letters compared to 12.3% in the sham-injection group (P<0.0001 for both groups) • 91.5% of patients in the sham group compared to 98.4% and 96.1% of patients in the ranibizumab 0.3 mg and 0.5 mg groups, respectively, lost <15 letters (P=0.0119 and P=0.1384, respectively) • There was a rapid improvement in vision within the first 7 days after treatment initiation in ranibizumab treated patients CFT decreased by 125.8 μm, 259.8 μm, and 270.7 μm in the sham and ranibizumab 0.3 mg and 0.5 mg groups, respectively (P<0.0001) |
| RESTORE26 | 345 | 1 year | Multicenter, randomized, double-masked, laser-controlled study | 1) Laser + sham injection 2) Ranibizumab + sham laser 3) Ranibizumab + laser |
• The mean change in BCVA was +6.8, +6.4, and +0.9 letters in the ranibizumab, ranibizumab + laser, and laser groups, respectively (P<0.0001 and P=0.0004, respectively) • A mean change in CRT of −118.7 μm and −128.3 μm in the ranibizumab and ranibizumab + laser groups, respectively, was significantly greater than in the laser group, −61.3 μm (P=0.0002 and P<0.0001, respectively) |
| DRCR.net33 | 854 | 1 year | Multicenter, randomized, controlled study | 1) Prompt laser + sham injection 2) Ranibizumab 0.5 mg + prompt laser 3) Ranibizumab 0.5 mg + deferred laser 4) Triamcinolone 4.0 mg + prompt laser |
• The mean change in BCVA was +9.0, +9.0, +4.0, and +3.0 in the ranibizumab + prompt laser, ranibizumab + deferred laser, triamcinolone + prompt laser, and sham + prompt laser groups, respectively (P<0.001, P<0.001, and P=0.31, respectively) • There was an insignificant change in CRT with a decrease of 131 μm, 137 μm, 127 μm, and 102 μm in the ranibizumab + prompt laser, ranibizumab + deferred laser, triamcinolone + prompt laser, and sham + prompt laser groups, respectively • Eyes treated with ranibizumab or triamcinolone, were less likely to have progression of diabetic retinopathy and vitreous hemorrhage |
Abbreviations: AMD, age-related macular degeneration; ATEs, arterial thromboembolic events; BCVA, best-corrected visual acuity; BRVO, branch retinal vein occlusion; CFT, central foveal thickness; CRVO, central retinal vein occlusion; CRT, central retinal thickness; DME, diabetic macular edema; FDA, US Food and Drug Administration; PDT, photodynamic therapy; PRN, pro re nata/“as needed”; RVO, retinal vein occlusion; SAE, serious adverse event; VA, visual acuity; ANCHOR, Anti-VEGF Antibody for the Treatment of Predominantly Classic Choroidal Neovascularization in AMD; BRAVO, Branch Retinal Vein Occlusion: Evaluation of Efficacy and Safety; CRUISE, Central Retinal Vein Occlusion Study: Evaluation of Efficacy and Safety; DRCR.net, Diabetic Retinopathy Clinical Research Network; HARBOR, A Study of Ranibizumab Administered Monthly or on an As-needed Basis in Patients with Subfoveal Neovascular Age-related Macular Degeneration; HORIZON, An Extension Study to Evaluate the Safety and Tolerability of Ranibizumab in Subjects with Choroidal Neovascularization Secondary to AMD; MARINA, Minimally Classic/Occult Trial of the Anti-VEGF Antibody Ranibizumab in the Treatment of Neovascular AMD; PIER, Phase IIIb, Multicenter, Randomized, Double-masked, Sham Injection Controlled Study of the Efficacy and Safety of Ranibizumab in Subjects with Subfoveal Choroidal Neovascularization (CNV) with or without Classic CNV Secondary to Age-related Macular Degeneration; RESTORE, Ranibizumab Monotherapy or Combined with Laser versus Laser Monotherapy for Diabetic Macular Edema; RIDE, Ranibizumab Injection in Subjects with Clinically Significant Macular Edema with Center Involvement Secondary to Diabetes Mellitus; RISE, Ranibizumab Injection in Subjects with Clinically Significant Macular Edema with Center Involvement Secondary to Diabetes Mellitus; SAILOR, Safety Assessment of Intravitreous Lucentis for AMD.