LUCENTIS (Page 6 of 7)

14.4 Diabetic Retinopathy (DR)

Efficacy and safety data of LUCENTIS are derived from Studies D-1 and D-2 [see Clinical Studies (14.3)] and D-3. All enrolled patients in Studies D-1 and D-2 had DR and DME at baseline. Study D-3 enrolled DR patients both with and without DME at baseline.

Of the 759 patients enrolled in Studies D-1 and D-2, 746 patients had a baseline assessment of fundus photography. Patients had baseline Early Treatment Diabetic Retinopathy Study Diabetic Retinopathy Severity Scores (ETDRS-DRSS) ranging from 10 to 75. At baseline, 62% of patients had non-proliferative diabetic retinopathy (NPDR) (ETDRS-DRSS less than 60) and 31% had proliferative diabetic retinopathy (PDR) (ETDRS-DRSS greater than or equal to 60). The ETDRS-DRSS could not be graded in 5% of patients at baseline, and 2% of patients had absent or questionable DR at baseline. Approximately 20% of the overall population had prior PRP.

After monthly treatment with LUCENTIS 0.3 mg, the following clinical results were observed (Table 7; Figure 7):

Table 7 ≥3-Step and ≥2-Step Improvement at Month 24 in Study D-1 and Study D-2
Outcome MeasureStudy *ShamLUCENTIS0.3 mgEstimated Difference(95% CI)
*
D-1: Sham, n=124; LUCENTIS 0.3 mg, n=117D-2: Sham, n=115; LUCENTIS 0.3 mg, n=117
Adjusted estimate based on stratified model
p < 0.05 for all time points comparing LUCENTIS 0.3 mg to sham from Month 12 through Month 24
§
p < 0.05 for all time points comparing LUCENTIS 0.3 mg to sham from Month 3 through Month 24
≥3-step improvement from baseline in ETDRS-DRSS D-12%17%15%(7%, 22%)
D-20%9%9%(4%, 14%)
≥2-step improvement from baseline in ETDRS-DRSS §D-14%39%35%(26%, 44%)
D-27%37%31%(21%, 40%)

At Month 24, DR improvement by ≥3-steps in ETDRS-DRSS from baseline in subgroups examined (e.g., age, gender, race, baseline visual acuity, baseline HbA1c, prior DME therapy at baseline, baseline DR severity (NPDR, PDR)) were generally consistent with the results in the overall population.

The difference in the proportion of patients treated with LUCENTIS 0.3 mg compared to sham who achieved DR improvement based on the ETDRS-DRSS was observed as early as Month 3 for ≥2-step improvement or at Month 12 for ≥3-step improvement.

Figure 7 Proportion of Patients with ≥ 3-Step and ≥ 2-Step Improvement from Baseline in ETDRS Diabetic Retinopathy Severity Level over Time in Study D-1 and Study D-2
≥3-Step Improvement from Baseline Over Time ≥2-Step Improvement from Baseline Over Time
Figure 7
(click image for full-size original)

Study D-3 enrolled DR patients with and without DME; 88 (22%) eyes with baseline DME and 306 (78%) eyes without baseline DME and balanced across treatment groups. Study D-3 was a randomized, active-controlled study where patient age ranged from 20 to 83 with a mean age of 51 years. A total of 394 study eyes from 305 patients, including 89 who had both eyes randomized, were enrolled (LUCENTIS, 191 study eyes; pan-retinal photocoagulation; 203 study eyes). All eyes in the LUCENTIS group received a baseline 0.5 mg intravitreal injection followed by 3 monthly intravitreal injections, after which treatment was guided by pre-specified re-treatment criteria. Patients had baseline ETDRS-DRSS ranging from 20 to 85. At baseline, 11% of eyes had NPDR (ETDRS-DRSS less than 60), 50% had mild-to-moderate PDR (ETDRS-DRSS equal to 60, 61, or 65), and 37% had high-risk PDR (ETDRS-DRSS greater than or equal to 71).

An analysis of data from Study D-3 demonstrated that at Year 2 in the LUCENTIS group, 31.7% and 28.4% of eyes in the subgroups with baseline DME and without baseline DME, respectively, had ≥ 3-step improvement from baseline in ETDRS-DRSS.

Table 8 Proportion of Eyes with ≥ 3-Step and ≥ 2-Step Improvement from Baseline in ETDRS-DRSS at Year 2 in Study D-3
LUCENTIS group
Outcome Measure(in ETDRS-DRSS)Eyes with Baseline DMEn = 41Eyes without Baseline DMEn = 148
≥ 3-step improvement from baseline95% CI for percentage13 (31.7%)(17.5%, 46.0%)42 (28.4%)(21.1%, 35.6%)
≥ 2-step improvement from baseline95% CI for percentage24 (58.5%)(43.5%, 73.6%)56 (37.8%)(30.0%, 45.7%)
Figure 8 Proportion of Eyes in the LUCENTIS group with ≥ 3-Step and ≥ 2-Step Improvement from Baseline in ETDRS-DRSS at Year 1 and Year 2 in Study D-3
Figure 8
(click image for full-size original)

14.5 Myopic Choroidal Neovascularization (mCNV)

The efficacy and safety data of LUCENTIS were assessed in a randomized, double-masked, active-controlled 3-month study in patients with mCNV. Patients age ranged from 18 to 87 years, with a mean age of 55 years. A total of 276 patients (222 patients in the LUCENTIS treated Groups I and II; 55 patients in the active control PDT group) were enrolled. Patients randomized to the LUCENTIS groups received injections guided by pre-specified re-treatment criteria. The retreatment criteria in Group I were vision stability guided, with the Best Corrected Visual Acuity (BCVA) at the current visit being assessed for changes compared with the two preceding monthly BCVA values. The retreatment criteria in Group II were disease activity guided, based on BCVA decrease from the previous visit that was attributable to intra- or sub-retinal fluid or active leakage secondary to mCNV as assessed by OCT and/or FA compared to the previous monthly visit.

Visual gains for the two LUCENTIS 0.5 mg treatment arms were superior to the active control arm. The mean change in BCVA from baseline at Month 3 was: +12.1 letters for Group I, +12.5 letters for Group II and +1.4 letters for the PDT group. (Figure 9; Table 9). Efficacy was comparable between Group I and Group II.

Table 9 Mean Change in Visual Acuity and Proportion of Patients who Gained ≥15 letters from Baseline at Month 3
Study ArmsMean change in BCVA from baseline (Letters)Proportion of patients who gained ≥15 letters from baseline
Mean (SD)Estimated Difference(95% CI)*PercentEstimated Difference(95% CI)*
*
Adjusted estimates based on stratified models; p < 0.01
Group I12.1 (10.2)10.9(7.6, 14.3)37.122.6(9.5, 35.7)
Group II12.5 (8.8)11.4(8.3, 14.5)40.526.0(13.1, 38.9)
Control (PDT)1.4 (12.2)14.5
Figure 9 Mean Change in Visual Acuity from Baseline to Month 3 in mCNV Study
Figure 9
(click image for full-size original)

The proportion of patients who gained ≥15 letters (ETDRS) by Month 3 was 37.1% and 40.5% for LUCENTIS Groups I and II, respectively and 14.5% for the PDT group. The mean number of injections between baseline and Month 3 was 2.5 and 1.8 for Groups I and II, respectively. 41% of patients received 1, 2 or 3 injections between baseline and Month 3 with no injections afterwards.

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