Ranibizumab, a humanized monoclonal antibody fragment inhibits multiple biologically active isoforms of vascular endothelial growth factor (VEGF)-A, (Ferrara et al. 2006) and is approved for the treatment of neovascular age-related macular degeneration (nAMD) in many countries around the world. Benefit of ranibizumab treatment in improving best-corrected visual acuity (BCVA) has been shown mainly in the Caucasian patient population (Rosenfeld et al. 2006; Brown et al. 2009), with some evidence in the Japanese nAMD patients (Tano & Ohji 2010). EXTEND III is the first clinical trial in South Korean and Taiwanese patients with subfoveal choroidal neovascularization secondary to AMD, including all lesion subtypes (predominantly classic, minimally classic and occult with no classic component). In this 12-month, open-label, single-arm, multicentre, Phase 3 study, patients received monthly intravitreal injections of ranibizumab 0.5 mg. Here, we report the mean change in BCVA from baseline to Month 4 (primary efficacy endpoint), and safety over this time period.
Of 95 enrolled patients (South Korea: 44 and Taiwan: 51) with a mean age of 71.2 years and a mean BCVA of 55.2 letters at baseline, 94 completed the Month 4 visit, whereas 1 patient discontinued owing to violation of exclusion criteria. At Month 4, there were significant improvements in the mean change ± standard error in BCVA from baseline by 9.3 ± 1.0 letters (in Taiwanese patients: 10.1 ± 1.6 and South Korean patients: 8.3 ± 1.2, both p < 0.0001, Fig. 1). The mean change in BCVA profile from baseline to Month 4 is comparable with that observed in the EXTEND I study (Tano & Ohji 2010). In EXTEND III 90.5% patients avoided BCVA loss (gain ≥0 letters). Additionally, 65.3% and 27.4% of the patients had a VA gain of ≥5 and ≥15 letters, respectively, while 98.9% of the patients lost <15 letters.
Patients received a mean ± standard deviation of 4.9 ± 0.48 injections over the 4-month treatment period. Overall, 33.7% (n = 32/95) patients experienced ocular adverse events (AEs); main ocular AEs were conjunctival haemorrhage (8.4%), retinal exudates (4.2%), and retinal haemorrhage (4.2%). Ocular AEs considered to be related to the study drug were cataract, conjunctival haemorrhage, retinal haemorrhage, reduced VA, vitreous floaters, injection-site pain and increased intraocular pressure (1.1% each). There were no Grade 3 targeted AEs reported during the 4-month period. Overall, 28.4% (n = 27/95) patients experienced nonocular AEs; the main nonocular AEs included nasopharyngitis and prostate cancer (4.2% each). Three patients reported AEs potentially related to systemic VEGF inhibition (hypertension [2.1%] and nonocular haemorrhage [1.1%]). There were no ocular serious AEs (SAEs) reported during the 4-month period. Nonocular SAEs were reported in 10 (10.5%) patients, of them only 1 (1.1%) was considered related to the study drug (blood pressure inadequately controlled). There were no deaths and discontinuations because of AEs. There were no new safety concerns observed during the 4 months of the study. The safety profiles between Taiwanese and South Korean patients were similar.
In conclusion, the results of the EXTEND III study indicate that after 4 months of treatment, ranibizumab therapy is effective and well tolerated in South Korean and Taiwanese nAMD patients.