MARINA and ANCHOR: Subgroup Analyses 1Year Data

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MARINA and ANCHOR Subgroup Analyses (1-Year
Data)

• Jennifer I. Lim, MD
• Doheny Eye Institute
• University of Southern California
• Los Angeles, CA
• April 30, 2007

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LUCENTIS (ranibizumab injection) Indication

• Choroidal neovascularization (CNV) is VEGF
  dependent
• LUCENTIS is a monoclonal antibody fragment that
  binds VEGF with high affinity
• Dosing 0.5 mg in 0.05 ml intravitreal injection
  monthly
• Efficacy shown for treatment of patients with CNV
  (wet) age-related macular degeneration

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Two Pivotal Phase III Lucentis Trials in
Neovascular AMD
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Subject Demographicsand Baseline Characteristics
Regraded as drusenoid PED and no CNV
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Subjects Losing lt15 Letters from Baseline
MARINA at month 12
ANCHOR at month 12
96
95
95
94
62
64
of subjects
of subjects
Sham (n238)
LUCENTIS 0.5 mg (n240)
LUCENTIS 0.3 mg (n238)
PDT (n143)
LUCENTIS 0.5 mg (n139)
LUCENTIS 0.3 mg (n140)
Month 12 was the primary endpoint in both
trials, month 24 was a secondary
endpoint.Plt0.01 vs sham Plt0.01 vs PDT
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Subgroup Analysis of Subjects Losing lt15
letters at Month 12
Age at Baseline
50 to 64 yrs
65 to 74 yrs
100
100
75 to 84 yrs
95
95
94
94
94
92
85 yrs
69
62
54
of subjects in each subgroup
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Sham
Ranibizumab0.3 mg
Ranibizumab0.5 mg
n 11 67 132 28 13 64
130 31 16 64 124 36
Plt0.001, Plt0.0001, Plt0.01 vs sham.
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Subgroup Analysis of Subjects Losing lt15
letters at Month 12
VA at Baseline (Snellen equivalent)
98
97
96
95
94
94
93
91
86
20/160 or worse
20/100 to 20/125
62
20/63 to 20/80
54
53
20/50 or better
of subjects in each subgroup
Sham
Ranibizumab0.3 mg
Ranibizumab0.5 mg
n 51 50 72 65 58 50
75 55 48 59 68 65
Plt0.0001 vs sham.
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Subgroup Analysis of Subjects Losing lt15
letters at Month 12
CNV Lesion Area at Baseline
2 DA
98
97
97
95
95
94
gt2 to 4 DA
92
86
gt4 to 6 DA
gt6 DA
67
64
63
55
of subjects in each subgroup
Sham
Ranibizumab0.3 mg
Ranibizumab0.5 mg
n 46 78 59 55 39
95 60 44 39 86 63
52
Plt0.001, Plt0.0001 vs sham.
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Subgroup Analysis of Subjects Losing lt15
letters at Month 12
Age at Baseline
Plt0.05, Plt0.0001 vs PDT
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Subgroup Analysis of Subjects Losing lt15
letters at Month 12
VA at Baseline (Snellen Equivalent)
Plt0.05, Plt0.01, Plt0.0001 vs PDT
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Subgroup Analysis of Subjects Losing lt15
letters at Month 12
CNV Lesion Area at Baseline
Plt.05, Plt.001 , Plt.0001 vs PDT
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Key Ocular Serious Adverse Events
One case also reported as uveitis by
investigator One subject had 2 episodes.
Cumulative through month 24 non-serious AE of
retinal tear in 7 subjects 2 (sham), 2 (0.3 mg)
and 3 (0.5 mg). Same subject had 2 episodes each
reported as uveitis and received systemic
antibiotics once Same subject had 2 episodes
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Key Systemic Safety Findings MARINA Year 2 and
ANCHOR Year 1
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Conclusions

• Subanalyses revealed no significant difference
  among subgroups in reaching the primary endpoint
  of losing lt15 letters
• Age at baseline
• VA at baseline
• CNV lesion area at baseline
• CNV lesion type at baseline
• Ranibizumab resulted in significant increases in
  the percent of patients who lost lt15 letters over
  1 year compared to sham and PDT
• The safety of ranibizumab was demonstrated by the
  low rates of ocular and non-ocular adverse events
  in both the MARINA and ANCHOR trials