COLUMBUS-AMD is a multicenter, parallel-group, 48-week phase III clinical trial that assessed the equivalence of FYB201, a candidate biosimilar for ranibizumab, with reference ranibizumab.
Study design
Patients with newly diagnosed, treatment-naïve active choroidal neovascularization secondary to age-related macular degeneration (AMD) with best-corrected visual acuity (BCVA) between 20/32 and 20/100 were randomized 1:1 to the 2 treatment arms and treated monthly. The primary endpoint of the study was change from baseline BCVA at 8 weeks.
Outcomes
A total of 477 patients from sites across Eastern and Western Europe were enrolled. From baseline to week 8, mean change in BCVA improved in both treatment groups (+5.1 Early Treatment Diabetic Retinopathy Study [ETDRS] letters for the FYB201 group and +5.6 ETDRS letters for the reference ranibizumab group), and the primary endpoint was met. At week 48, mean change in BCVA was +7.8 and +8.0 ETDRS letters, respectively. Ocular adverse events, including intraocular inflammations, were comparable between the groups.
Limitations
This was a well-designed study with few limitations. Of note, the study was conducted outside of the United States; therefore, results will need to be extrapolated to the US population. In addition, only 83.8% of those in the FYB201 arm and 79.1% in the reference ranibizumab arm received all 12 injections.
Clinical significance
The study demonstrated the equivalence of FYB201 and reference ranibizumab in terms of efficacy, safety, and immunogenicity in neovascular AMD. Biosimilars have been approved in the European Union since 2006, and the first biosimilar was approved in the United States in 2015. Experience with biosimilars has demonstrated that they are safe and effective for their approved indications. The availability of biosimilars can increase price competition between products and potentially expand access to more patients. The question here is the utility of a biosimilar to ranibizumab when bevacizumab is available for use. Although bevacizumab is not approved in the United States for ophthalmic use, it is widely used and has been proven to be efficacious for neovascular AMD in randomized trials. Since retina specialists have a long track history and comfort level with bevacizumab, which has significant cost savings vs. ranibizumab, it is unclear what the impetus would be to try FYB201.