Efficacy and safety of a new ranibizumab biosimilar CKD-701 using a pro re nata treatment regimen in neovascular age-related macular degeneration: A phase 3 randomized clinical trial.

ABSTRACT

PURPOSE: This study aimed to establish the efficacy, safety, and immunogenicity equivalence of the proposed biosimilar CKD-701 with the reference ranibizumab in patients with treatment-naïve neovascular age-related macular degeneration (nAMD). PATIENTS AND METHODS: A total of 312 participants with active subfoveal choroidal neovascularization were randomly assigned to either the CKD-701 (n = 156) or reference ranibizumab (n = 156) arms. The initial 3-month loading intraocular injections were followed by pro re nata (PRN) dosing for 9 months. The primary outcome was the proportion of patients with less than 15-letters of corrected visual acuity (BCVA) loss at 3 months visit (one month after last loading injection) compared to the baseline time point. The presence of retinal fluid, and changes in BCVA and central retinal thickness (CRT) were assessed as secondary efficacy outcomes. Immunogenicity and safety were evaluated in both treatment arms. RESULTS: In the CKD-701 arm, 143 (97.95%) patients lost <15 letters in the BCVA at 3 months compared to 143 (98.62%) in the reference arm (P = 0.67). The BCVA improved with a mean improvement of +7.0 (CKD-701) and +6.2 (ranibizumab) letters at 3 months (P = 0.43). The least-squares mean (SE) changes in CRT at 3 months from the baseline were -119.3 (12.0) µm and -124.5 (11.9) µm in the CKD-701 and ranibizumab groups, respectively (P = 0.74). The proportion of participants with subretinal or intraretinal fluid at 3, 6, and 12 months was similar between the study arms. The number (SE) of injections were 8.36 (3.13) in the CKD-701 and 8.26 (2.92) in ranibizumab (P = 0.62). The occurrence of adverse events and antidrug antibody in the study arms were also not statistically different. CONCLUSION: CKD-701 is a biosimilar to the reference ranibizumab in terms of efficacy, safety, and immunogenicity for the treatment of patients with nAMD. Moreover, improvement and maintenance of visual outcome were achieved through PRN regimen.