Randomized Trial of Biosimilar ABP 938 Compared with Reference Aflibercept in Adults with Neovascular Age-related Macular Degeneration.

PURPOSE

To evaluate the clinical efficacy, safety, and immunogenicity of biosimilar ABP 938 compared with aflibercept reference product (RP) in adults with neovascular (wet) age-related macular degeneration (nAMD).

DESIGN

A randomized, double-masked, active-controlled, multiregional clinical study.

PARTICIPANTS

A total of 579 patients with active treatment-naïve choroidal neovascularization secondary to nAMD were randomized.

METHODS

Evaluable patients (N=576) received 2 mg of ABP 938 (n=288) or aflibercept RP (n=288) by intravitreal injection every 4 weeks for the first 3 doses, then every 8 weeks through week 48. At week 16, the ABP 938 group continued on ABP 938 (n=273), while the aflibercept RP group was re-randomized to continue on aflibercept RP (n=136) or transition to ABP 938 (n=134).

MAIN OUTCOME MEASURES

The primary efficacy endpoint was the least squares mean difference in change in best-corrected visual acuity (BCVA), measured by Early Treatment Diabetic Retinopathy Study letter score, from baseline to week 8. Secondary efficacy endpoints, safety, and immunogenicity were analyzed descriptively. In a substudy of patients, serum drug concentration profiles were assessed.

RESULTS

Demographic and baseline characteristics and exposure to treatment were similar between groups. Among initially randomized patients, the least squares mean difference in change from baseline in BCVA at week 8 between ABP 938 and aflibercept RP was 0.1, with a 2-sided 95% confidence interval (CI, -1.3, 1.5), and 90% CI (-1.1, 1.3) falling within pre-specified similarity margins (-3.9, 3.9 and -3, 3, respectively); thus, the primary clinical efficacy endpoint was met. Secondary efficacy endpoints (parallel-arm and post-transition) were overall similar between groups. No clinically meaningful differences were observed in the incidence of ocular and non-ocular adverse events, or events of interest. A low and similar incidence of binding antidrug antibodies was observed in all groups. The substudy confirmed low systemic exposure of free drug concentrations of ABP 938 and aflibercept RP.

CONCLUSIONS

This study supports a conclusion of no clinically meaning differences in efficacy, safety, and immunogenicity between ABP 938 and aflibercept RP in patients with nAMD. Additionally, transitioning from aflibercept RP to APB 938 at week 16 were comparable overall efficacy, safety, and immunogenicity to the continuous-treatment groups.