ly as every 4 weeks starting from Week 52 to Week 88
G) In GALILEO study, both control group and Eylea 2mg patients received Eylea 2 mg on an as-needed basis every 8 weeks starting from Week 52 to Week 68.
Figure 2: Mean change from baseline to week 52 in visual acuity by treatment group for the COPERNICUS and GALILEO studies (Full Analysis Set)
The proportion of perfused patients in the Eylea group was high in the GALILEO study at baseline (86.4%; n = 89). Perfusion at week 24 primary endpoint was 91.8% (n = 89). The patients were largely able to maintain their perfusion status until week 76 (84.3%; n = 75). The number of perfused patients that started on sham was 79.4% (n = 54) at baseline. Perfusion at week 24 primary endpoint was 85.5% (n = 47). Patients in the sham group were switched to Eylea according to pre-specified criteria at week 52, 83,7% (n = 41) were perfused at this time. The patients were able to maintain their perfusion status until week 76 (84.0%; n = 42).
The proportion of perfused patients in the Eylea group in the COPERNICUS study at baseline was 67.5% (n = 77). Perfusion at week 24 primary endpoint was 87.4%; (n = 90). After week 24, patients in the Eylea group were treated according to pre-specified criteria. At week 100 76.8 % (n = 76) of patients were perfused. The percentage of perfused patients that started on sham was 68.5% (n = 50) at baseline. Perfusion at week 24 primary endpoint was 58.6% (n = 34). Patients in the sham arm were eligible to receive Eylea from week 24. The proportion of perfused patients increased to 83.9% (n = 47) at week 52 and was largely maintained until week 100 (78%; n = 39).
The beneficial effect of Eylea treatment on visual function was similar in the baseline subgroups of perfused and non-perfused patients.
In combined data analysis of the GALILEO and COPERNICUS studies, Eylea demonstrated clinically meaningful changes from baseline in pre-specified secondary efficacy endpoint National Eye Institute Visual Function Questionnaire (NEI VFQ-25). The magnitude of these changes was similar to that seen in published studies, which corresponded to a 15-letter gain in Best Corrected Visual Acuity (BCVA).
Treatment effects in all eva luable subgroups (e.g. age, gender, race, baseline visual acuity, retinal perfusion status, CRVO duration) in each study were in general consistent with the results in the overall populations.
Elderly population
In the CRVO studies, approximately 52% (112/217) of the patients randomised to treatment with Eylea were 65 years of age or older, and approximately 18% (38/217) were 75 years of age or older.
Paediatric population
The European Medicines Agency has waived the obligation to submit the results of studies with Eylea in all subsets of the paediatric population in wet AMD and CRVO (see section 4.2 for information on paediatric use).
5.2 Pharmacokinetic properties
Eylea is administered directly into the vitreous to exert local effects in the eye.
Absorption / Distribution
Aflibercept is slowly absorbed from the eye into the systemic circulation after intravitreal administration and is predominately observed in the systemic circulation as an inactive, stable complex with VEGF; however only “free aflibercept” is able to bind endogenous VEGF.
In a pharmacokinetic sub-study in 6 patients with frequent sampling, maximum plasma concentrations of free aflibercept (systemic Cmax) were low, with a mean of approximately 0.02 microgram/ml (range 0 to 0.054) within 1 to 3 days after a |
