Efficacy and Safety of the Aflibercept Biosimilar SB15 in Neovascular Age-Related Macular Degeneration: A Phase 3 Randomized Clinical Trial
Jazyk angličtina Země Spojené státy americké Médium print
Typ dokumentu randomizované kontrolované studie, klinické zkoušky, fáze III, časopisecké články, práce podpořená grantem
PubMed
37289448
PubMed Central
PMC10251242
DOI
10.1001/jamaophthalmol.2023.2260
PII: 2805760
Knihovny.cz E-zdroje
- 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
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.
Albert Szent Györgyi Medical Center University of Szeged Szeged Hungary
Bajcsy Zsilinszky Korhaz es Rendelointezet Budapest Hungary
Department of Ophthalmology Axon Clinical Praha Czech Republic
Department of Ophthalmology Clinical Center University of Debrecen Debrecen Hungary
Department of Ophthalmology Doheny Eye Institute Pasadena California
Department of Ophthalmology Gabinet Okulistyczny Katowice Poland
Department of Ophthalmology Korea University Ansan Hospital Ansan Republic of Korea
Department of Ophthalmology Rydygier Memorial Hospital Krakow Poland
Department of Ophthalmology Seoul National University Bundang Hospital Seoul Republic of Korea
Department of Ophthalmology University Hospital Hradec Kralove Hradec Kralove Czech Republic
Department of Ophthalmology University of Pécs Medical School Pécs Hungary
Department of Ophthalmology Yeungnam University College of Medicine Daegu Republic of Korea
Pavlov 1st State Medical University of St Petersburg St Petersburg Russia
Retina Research Institute of Texas Abilen
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ClinicalTrials.gov
NCT04450329
