Comparability of aflibercept biosimilar with reference aflibercept in diabetic macular edema: subgroup analysis of the pivotal Phase-III INSIGHT randomized clinical trial

BACKGROUND: Phase-III INSIGHT study subgroup analyses observed best corrected visual acuity (BCVA) and central subfield thickness (CST) outcomes at Week 8/52 in diabetic macular edema treated with aflibercept biosimilar (MYL-1701P/Yesafili™) or reference aflibercept (Eylea®). RESEARCH DESIGN AND METHODS: = 176) was given intravitreally every 4 weeks for 5 doses, followed by 8-weekly dosing through Week 48. Subgroups were stratified by baseline BCVA/baseline CST/age/gender/race/ethnicity/region/glycated hemoglobin (HbA1c)/anti-drug antibody status/anti-vascular endothelial growth factor therapy in fellow eye. Main outcome measures included mean change in BCVA/CST from baseline to Week 8/52 with 90% confidence interval (CI). RESULTS: For MYL-1701P and reference aflibercept, participants with baseline BCVA score (73-55 letters) had an adjusted mean difference of 0.03 letters in BCVA (90% CI: -1.26,1.31) and 15.46 µm in CST (90% CI: -0.02,30.93) at 8 weeks and 0.81 letters in BCVA (90% CI: -0.58,2.2) and 6.41 µm in CST (90% CI: 17.31,30.12) at 52 weeks. Subgroup categories with ≥45% participants, including CST (<400/≥400 µm) and HbA1c (<8%/>8%) had an adjusted mean difference within -3 to 3 letters (90% CI) in BCVA at 8/52 weeks. CONCLUSIONS: The exploratory subgroup analyses supported clinical equivalence between MYL-1701P and reference aflibercept showing clinically comparable changes in BCVA/CST across most subgroups. TRIAL REGISTRATION: ClinicalTrials.gov identifier is NCT03610646.