IMPORTANCE: Aflibercept biosimilars can expand available treatment options in retinal diseases and have the potential to improve patient access to safe and effective therapy. OBJECTIVE: To establish equivalence in efficacy and similarity in safety, pharmacokinetics, and immunogenicity of SB15 and reference aflibercept (AFL) in neovascular age-related macular degeneration (nAMD). DESIGN, SETTING, AND PARTICIPANTS: This was a randomized double-masked parallel group phase 3 trial conducted at 56 centers in 10 countries from June 2020 to March 2022, including follow-up through 56 weeks. Of 549 screened participants, 449 participants 50 years and older with treatment-naive nAMD were included and randomly assigned to SB15 (n = 224) or AFL (n = 225). Key exclusion criteria included considerable scarring, fibrosis, atrophy, and hemorrhage. This report includes results up to the end of the parallel group period at week 32. Of the 449 randomized participants, 438 (97.6%) completed week 32 follow-up. INTERVENTION: Participants were randomized 1:1 to receive 2 mg of SB15 or AFL every 4 weeks for the first 12 weeks (3 injections), followed by dosing every 8 weeks up to week 48, with final assessments at week 56. MAIN OUTCOMES AND MEASURES: The primary end point was the change in best-corrected visual acuity (BCVA) from baseline to week 8 with predefined equivalence margins of -3 letters to 3 letters. Other key end points were changes in BCVA and central subfield thickness up to week 32, safety, pharmacokinetics, and immunogenicity. RESULTS: The mean (SD) age among the 449 included participants was 74.0 (8.1) years, and 250 participants (55.7%) were female. Baseline demographic characteristics and most disease characteristics were comparable between treatment groups. The least squares mean change in BCVA from baseline to week 8 in the SB15 group was equivalent to that in the AFL group (6.7 letters vs 6.6 letters, respectively; difference, 0.1 letters; 95% CI, -1.3 to 1.4). Comparable efficacy between treatment groups was maintained up to week 32 (least squares mean change from baseline in BCVA: SB15, 7.6 letters vs AFL, 6.5 letters; least squares mean change from baseline in central subfield thickness: SB15, -110.4 μm vs AFL, -115.7 μm). No clinically relevant differences were observed in the incidence of treatment-emergent adverse events (TEAEs) (SB15, 107/224 [47.8%] vs AFL, 98/224 [43.8%]) and ocular TEAEs in the study eye (SB15, 41/224 [18.3%] vs AFL, 28/224 [12.5%]). The serum concentration profiles and cumulative incidences of overall antidrug antibody positive participants were comparable. CONCLUSIONS AND RELEVANCE: In this phase 3 randomized clinical trial, SB15 and AFL showed equivalent efficacy and comparable safety, pharmacokinetics, and immunogenicity in participants with nAMD. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04450329.

• MeSH
• biosimilární léčivé přípravky * škodlivé účinky   MeSH
• inhibitory angiogeneze škodlivé účinky   MeSH
• injekce intravitreální MeSH
• lidé MeSH
• makulární degenerace * farmakoterapie   MeSH
• ranibizumab terapeutické užití   MeSH
• receptory vaskulárního endoteliálního růstového faktoru terapeutické užití   MeSH
• rekombinantní fúzní proteiny škodlivé účinky   MeSH
• senioři MeSH
• vlhká makulární degenerace * diagnóza   farmakoterapie   chemicky indukované   MeSH
• výsledek terapie MeSH
• zraková ostrost MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze III MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH
• Názvy látek
• aflibercept MeSH Prohlížeč
• biosimilární léčivé přípravky * MeSH
• inhibitory angiogeneze MeSH
• ranibizumab MeSH
• receptory vaskulárního endoteliálního růstového faktoru MeSH
• rekombinantní fúzní proteiny MeSH

BACKGROUND/AIMS: To provide longer-term data on efficacy, safety, immunogenicity and pharmacokinetics (PK) of ranibizumab biosimilar SB11 compared with the reference ranibizumab (RBZ) in patients with neovascular age-related macular degeneration (nAMD). METHODS: Setting: Multicentre. Design: Randomised, double-masked, parallel-group, phase III equivalence study. Patient population: ≥50 years old participants with nAMD (n=705), one 'study eye'. INTERVENTION: 1:1 randomisation to monthly intravitreal injection of 0.5 mg SB11 or RBZ. Main outcome measures: Visual efficacy endpoints, safety, immunogenicity and PK up to 52 weeks. RESULTS: Baseline and disease characteristics were comparable between treatment groups. Of 705 randomised participants (SB11: n=351; RBZ: n=354), 634 participants (89.9%; SB11: n=307; RBZ: n=327) completed the study until week 52. Previously reported equivalence in primary efficacy remained stable up to week 52 and were comparable between SB11 and RBZ. The adjusted treatment difference between SB11 and RBZ in full analysis set at week 52 of change from baseline in best-corrected visual acuity was -0.6 letters (90% CI -2.1 to 0.9) and of change from baseline in central subfield thickness was -14.9 µm (95% CI -25.3 to -4.5). The incidence of ocular treatment-emergent adverse events (TEAEs) (SB11: 32.0% vs RBZ: 29.7%) and serious ocular TEAE (SB11: 2.9% vs RBZ: 2.3%) appeared comparable between treatment groups, and no new safety concerns were observed. The PK and immunogenicity profiles were comparable, with a 4.2% and 5.5% cumulative incidence of antidrug antibodies up to week 52 for SB11 and RBZ, respectively. CONCLUSIONS: Longer-term results of this study further support the biosimilarity established between SB11 and RBZ.

• Klíčová slova
• degeneration, macula, neovascularisation, retina,
• MeSH
• biosimilární léčivé přípravky * terapeutické užití   MeSH
• inhibitory angiogeneze terapeutické užití   MeSH
• injekce intravitreální MeSH
• lidé středního věku MeSH
• lidé MeSH
• makulární degenerace * farmakoterapie   MeSH
• ranibizumab terapeutické užití   MeSH
• vaskulární endoteliální růstový faktor A MeSH
• vlhká makulární degenerace * diagnóza   farmakoterapie   MeSH
• výsledek terapie MeSH
• zraková ostrost MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze III MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH
• Názvy látek
• biosimilární léčivé přípravky * MeSH
• inhibitory angiogeneze MeSH
• ranibizumab MeSH
• vaskulární endoteliální růstový faktor A MeSH