Results of a subgroup analysis of Japanese wet AMD patients participating in the VIEW2 intravitreal aflibercept study has shown that the treatment is as well tolerated and effective in the Japanese wet AMD population as in the full VIEW 2 study population. Despite the existence of unique characteristics in the Japanese wet AMD phenotype, the subgroup analysis among 101 Japanese patients demonstrated that the overall results of the 1,240 patient VIEW 2 study are representative of wet AMD in the Japanese group studied. The main VIEW2 study had randomised 1,240 wet AMD patients at 172 sites in Europe, the Middle East, Asia-Pacific, and Latin America in a 1:1:1:1 ratio of the following regimens: 0.5 mg IVT-AFL every 4 weeks (0.5q4); 2 mg IVT-AFL every 4 weeks (2q4); 2 mg IVT-AFL every 8 weeks (2q8) after three injections at weeks 0, 4 and 8; or, 0.5 mg ranibizumab every 4 weeks (Rq4). The primary endpoint analysis was non-inferiority of IVT-AFL to ranibizumab in the proportion of patients maintaining vision at week 52. Efficacy results published in November 2014 showed that visual function outcomes were similar across all NEI VFQ-25 subscales over 52 weeks for intravitreal aflibercept 2q8 and ranibizumab 0.5q4, with clinically meaningful improvement recorded in 6 of 12 subscales (Ophthalmology. 2014 Nov 6. pii: S0161-6420(14)00902-6. doi: 10.1016/j.ophtha.2014.09.024).
The research, undertaken at the Department of Ophthalmology and Visual Science, Nagoya City University Graduate School of Medical Sciences, Japan, showed that all the Japanese patients in the aflibercept-treated groups (n=70) maintained vision compared to 96% of Japanese patients treated with ranibizumab. At week 52, Japanese patients in all treatment groups showed improvement in BCVA following treatment. Similar BCVA gains recorded for patients treated with the Rq4 regimen (0.5 mg ranibizumab every 4 weeks), 2q4 regimen (2 mg aflibercept every 4 weeks) and 2q8 regimen (2 mg aflibercept every 8 weeks, after three injections at weeks 0, 4 and 8). The 0.5q4 regimen group (0.5 mg aflibercept every 4 weeks) had higher gains referable to an unexpected drop in BCVA between screening and baseline. In addition, central retinal thickness (CRT) and mean area of choroidal neovascularisation decreased similarly in all treatment groups while adverse events were balanced across treatment groups.
Interest in conducting a specific subgroup analysis with Japanese patients arises from the observation of several unique characteristics noted among wet AMD patients from Japan. These include a higher than expected incidence of the disease in Japanese males vs. females, a low incidence of large drusen on fundus examination, a higher incidence of unilateral involvement, a high rate of polypoidal choroidal vasculopathy (PCV) and a lower rate of retinal angiomatous proliferation. In addition, detachment of the retinal pigment epithelium (RPE) and major haemorrhage have been found to be common among Japanese wet AMD patients, while drusen in the fellow eye appears to be uncommon. Finally, differences in risk alleles have been reported in Japanese patients, compared to other populations, and as such, wet AMD has a somewhat different presentation. Notwithstanding the phenotypic differences compared to a white population, treatment with aflibercept, at least in respect of the VIEW2 trial results, appear to have a similar effect on the course of the disease as was observed in the rest of the VIEW2 study population.