. After an initial increase in visual acuity (following monthly dosing), on average, patients' visual acuity declined with quarterly dosing, returning to baseline at Month 12 and this effect was maintained in most ranibizumab-treated patients (82%) at Month 24. Data from a limited number of subjects that crossed over to receive ranibizumab after more than a year of sham-treatment suggested that early initiation of treatment may be associated with a better preservation of visual acuity.
In both the MARINA and ANCHOR studies, the improvement in visual acuity seen with Lucentis 0.5 mg at 12 months was accompanied by patient-reported benefits as measured by the National Eye Institute Visual Function Questionnaire (VFQ-25) scores. The differences between Lucentis 0.5 mg and the two control groups were assessed with p-values ranging from 0.009 to <0.0001.
The efficacy of Lucentis in the treatment of wet AMD has been further confirmed in AMD studies finalised since the marketing approval. Data from two studies (MONT BLANC, BPD952A2308 and DENALI, BPD952A2309) did not demonstrate additional effect of the combined administration of verteporfin (Visudyne PDT) and Lucentis compared to Lucentis monotherapy.
Treatment of visual impairment due to DME
The efficacy and safety of Lucentis have been assessed in two randomised, double-masked, sham- or active controlled studies of 12 months duration in patients with visual impairment due to diabetic macular oedema. A total of 496 patients (336 active and 160 control) were enrolled in these studies, the majority had type II diabetes, 28 ranibizumab-treated patients had type I diabetes.
In the phase II study D2201 (RESOLVE), 151 patients were treated with ranibizumab (6 mg/ml, n=51, 10 mg/ml, n=51) or sham (n=49) by monthly intravitreal injections until pre-defined treatment stopping criteria were met. The initial ranibizumab dose (0.3 mg or 0.5 mg) could be doubled at any time during the study after the first injection. Laser photocoagulation was allowed as rescue treatment from Month 3 in both treatment arms. The study had two parts: an exploratory part (the first 42 patients analysed at Month 6) and a confirmatory part (the remaining 109 patients analysed at Month 12).
Key outcome measures from the confirmatory part of the study (2/3 of patients) are summarised in Table 3.
Table 3 Outcomes at Month 12 in study D2201 (RESOLVE) (overall study population)
Outcome measure
Ranibizumab pooled
(n=102)
Sham
(n=49)
Mean average change in BCVA from Month 1 to Month 12 compared to baselinea (letters) (SD) (primary endpoint)
+7.8 (7.72)
-0.1 (9.77)
Mean change in BCVA at Month 12a (letters) (SD)
+10.3 (9.14)
-1.4 (14.16)
Gain of ≥10 letters in BCVA (%) at Month 12a
60.8
18.4
Gain of ≥15 letters in BCVA (%) at Month 12
32.4
10.2
p-value
0.0043
ap<0.0001
In the phase III study D2301 (RESTORE), 345 patients with visual impairment due to macular oedema were randomised to receive either intravitreal injection of ranibizumab 0.5 mg as monotherapy and sham laser photocoagulation (n=116), combined ranibizumab 0.5 mg and laser photocoagulation (n=118), or sham injection and laser photocoagulation (n=111). Treatment with ranibizumab was started with monthly intravitreal injections and continued until visual acuity was stable for at least three consecutive monthly assessments. The tre |
