TY - JOUR
T1 - MERLIN
T2 - Phase 3a, Multicenter, Randomized, Double-Masked Trial of Brolucizumab in Participants with Neovascular Age-Related Macular Degeneration and Persistent Retinal Fluid
AU - MERLIN Investigators
AU - Khanani, Arshad M.
AU - Brown, David M.
AU - Jaffe, Glenn J.
AU - Wykoff, Charles C.
AU - Adiguzel, Eser
AU - Wong, Randall
AU - Meng, Xiangyi
AU - Heier, Jeffrey S.
N1 - Funding Information:
Supported by Novartis Pharmaceuticals Corporation, East Hanover, New Jersey. The author(s) have made the following disclosure(s): A.M.K.: Consultant – Adverum Biotechnologies, Aerpio Pharmaceuticals, Alimera Sciences, Allergan, Apellis Pharmaceuticals, AsclepiX Therapeutics, Aviceda Therapeutics, Bausch & Lomb, BroadWing Bio, Chengdu Kanghong Pharmaceutical, Cholgene Therapeutics, Dutch Ophthalmic Research Center, 4D Molecular Therapeutics, Gemini Pharmaceuticals, Genentech, Glaukos, Graybug Vision, Gyroscope Therapeutics, IVERIC bio, Janssen Pharmaceuticals, Kato Pharmaceuticals, Kodiak, Oculis, Opthea, Novartis, PolyPhotonix, RecensMedical, Regeneron Pharmaceuticals, REGENXBIO, Retrotope, Roche, Surrozen, Thea Pharma, UNITY Biotechnology; Financial support – Adverum Biotechnologies, Apellis Pharmaceuticals, AsclepiX Therapeutics, Chengdu Kanghong Biotechnology, Dutch Ophthalmic Research Center, 4D Molecular Therapeutics, Gemini Pharmaceuticals, Genentech, Graybug Vision, Gyroscope Therapeutics, IVERIC bio, Janssen Pharmaceuticals, Kodiak, Neurotech, NGM Biopharmaceuticals, Novartis, Ocular Therapeutix, Oculis, Opthea, RecensMedical, REGENXBIO, Roche, UNITY Biotechnology; Lecturer – Allergan, Genentech, Novartis; Equity owner – Aviceda Therapeutics, PolyPhotonix, RecensMedical, Retrotope D.M.B.: Consultant – Adverum Biotechnologies, Alexion Pharmaceuticals, Annexon Biosciences, Apellis Pharmaceuticals, Bayer, Boehringer Ingelheim, Celltrion, Chengdu Kanghong Biotechnology, Clearside Biomedical, Dark Horse Consulting, Horizon Therapeutics, Jefferies, Kodiak, Laboratoires Thea, Lineage Cell Therapeutics, Novartis, Ocular Therapeutix, Optos, Regeneron Pharmaceuticals, RetinAI Medical, Senju Pharmaceutical, Stealth BioTherapeutics, Verseon, Wedbush; Financial support – Adverum Biotechnologies, Aldeyra Therapeutics, Apellis Pharmaceuticals, Bayer, BIRC, Boehringer Ingelheim, Clearside Biomedical, Cleveland Clinic Foundation, F. Hoffmann-La Roche, Gyroscope Therapeutics, Ionis Pharmaceuticals, IVERIC bio, Kodiak, Lowy Medical Research Institute, LumiThera, Nanoscope Therapeutics, National Eye Institute/National Institutes of Health, NGM Biopharmaceuticals, Novartis, OIRRC, Optos, Oxurion, Regeneron Pharmaceuticals, REGENXBIO, Sam Chun Dang Pharm, Santen Pharmaceutical, Senju Pharmaceutical C.C.W.: Consultant – 4DMT, AbbVie, Adverum, Aerie, AGTC, Alimera, Allergan, Allgenesis, Alnylam, Annexon, Apellis, Bausch & Lomb, Bayer, Bionic Vision Technologies, Boehringer Ingelheim, Chengdu Kanghong Biotechnologies, Cholgene, Clearside, Curacle, EyePoint, Frontera, Genentech, Gyroscope, IACTA, IVERIC Bio, Janssen, Kato, Kiora, Kodiak, Kriya, Merck, Nanoscope, NGM, Novartis, OccuRx, Ocuterra, OliX, ONL, Opthea, Palatin, Perfuse, PolyPhotonix, Ray, RecensMedical, Regeneron, RegenXBio, Resonance, Roche, Stealth, Surrozen, THEA, TissueGen, Valo, Verana, Vitranu; Financial support – 4DMT, Adverum, Aerie, AffaMed, Aldeyra, Alexion, Alimera, Alkahest, Allergan, Amgen, Annexon, Apellis, AsclepiX, Bayer, Boehringer Ingelheim, Chengdu Kanghong Biotechnology, Clearside, Gemini, Genentech, Graybug Vision, Gyroscope, IONIS, iRENIX, IVERIC bio, Kodiak, LMRI, Nanoscope, Neurotech, NGM, Novartis, Ocular Therapeutix, Ocuphire, Opthea, Oxurion, Oyster Point, RecensMedical, Regeneron, RegenXBio, Roche, SamChunDang Pharm, Sandoz, Taiwan Liposome Company, UNITY, Verily, Xbrane BioPharma; Board member – American Society of Retina Specialists, Vit-Buckle Society; Equity owner – ONL, PolyPhotonix, RecensMedical, Visgenx, Vitranu J.S.H.: Consultant – Abpro, Adverum, Aerie, AffaMed, Allegro, Allergan, Allgenesis Biotherapeutics, Annexon Biosciences, Apellis Pharmaceuticals, Aprea Therapeutics, AsclepiX Therapeutics, Aviceda Therapeutics, Bionic Vision Technologies, Chengdu Kanghong Biotechnology, DTx Pharma, Eloxx Pharmaceuticals, 4D Molecular Therapeutics, Galimedix Therapeutics, Genentech/Roche, Graybug Vision, Gyroscope, Horizon Therapeutics, IVERIC bio, LensGen, NGM Biopharmaceuticals, Novartis, Ocular Therapeutix, Oriole, Oxurion, Palatin Technologies, Regeneron Pharmaceuticals, REGENXBIO, Roche, Santen Pharmaceutical, SciFluor Life Sciences, Stealth BioTherapeutics, Surrozen, Laboratoires Thea, Verseon, Vinci; Financial support – Apellis Pharmaceuticals, AsclepiX Therapeutics, Bayer, Chengdu Kanghong Biotechnology, Genentech/Roche, Gyroscope, Hemera Biosciences, IVERIC bio, Kodiak, NGM Biopharmaceuticals, Notal Vision, Novartis, Regeneron Pharmaceuticals, REGENXBIO, Stealth BioTherapeutics; Equity owner – Adverum, Aldeyra Therapeutics, Allegro, Aviceda Therapeutics, Digital Surgery Systems, DTx Pharma, jCyte, Ocular Therapeutix, Vinci Obtained funding: N/A
Publisher Copyright:
© 2022
PY - 2022/9
Y1 - 2022/9
N2 - PURPOSE: To assess the 52-week efficacy and safety of brolucizumab 6 mg administered every 4 weeks compared with aflibercept 2 mg dosed every 4 weeks in eyes with neovascular age-related macular degeneration (nAMD) and persistent retinal fluid.DESIGN: Multicenter, randomized, double-masked phase 3a study.PARTICIPANTS: Participants with recalcitrant nAMD (persistent residual retinal fluid despite previous frequent anti-vascular endothelial growth factor treatment).METHODS: Eyes were randomized (2:1) to intravitreal brolucizumab 6 mg or aflibercept 2 mg every 4 weeks up to and including week 100.MAIN OUTCOME MEASURES: The primary end point was analysis of noninferiority in mean best-corrected visual acuity (BCVA) change from baseline to week 52 (margin, 4 letters). Other key end points included change in central subfield thickness (CST) from baseline to week 52, fluid-free status (no intraretinal fluid and no subretinal fluid), and safety.RESULTS: At week 52, brolucizumab was noninferior to aflibercept in BCVA change from baseline (least squares mean difference, -0.6 Early Treatment Diabetic Retinopathy Study letters; 95% confidence interval [CI], -2.1 to 0.9; P < 0.001). A total of 4.8% and 1.7% of participants reported a 15-letter or more BCVA loss from baseline at week 52 in the brolucizumab and aflibercept groups, respectively. In eyes treated with brolucizumab compared with those treated with aflibercept, the CST was reduced significantly (P < 0.001), and a significantly greater proportion of eyes were fluid free at week 52 (40.4% brolucizumab vs. 19.0% aflibercept; 95% CI, 13.9-29.0; P < 0.001). Incidence of intraocular inflammation (IOI), including retinal vasculitis and retinal vascular occlusion, were 9.3% (0.8% and 2.0%) for brolucizumab versus 4.5% (0% and 0%) for aflibercept, respectively.CONCLUSIONS: Visual acuity outcomes in previously treated participants with nAMD and persistent retinal fluid receiving brolucizumab 6 mg dosed every 4 weeks were noninferior to aflibercept 2 mg dosed every 4 weeks, with superior anatomic outcomes. However, incidences of IOI, including retinal vasculitis and retinal vascular occlusion, also were higher, leading to study termination.
AB - PURPOSE: To assess the 52-week efficacy and safety of brolucizumab 6 mg administered every 4 weeks compared with aflibercept 2 mg dosed every 4 weeks in eyes with neovascular age-related macular degeneration (nAMD) and persistent retinal fluid.DESIGN: Multicenter, randomized, double-masked phase 3a study.PARTICIPANTS: Participants with recalcitrant nAMD (persistent residual retinal fluid despite previous frequent anti-vascular endothelial growth factor treatment).METHODS: Eyes were randomized (2:1) to intravitreal brolucizumab 6 mg or aflibercept 2 mg every 4 weeks up to and including week 100.MAIN OUTCOME MEASURES: The primary end point was analysis of noninferiority in mean best-corrected visual acuity (BCVA) change from baseline to week 52 (margin, 4 letters). Other key end points included change in central subfield thickness (CST) from baseline to week 52, fluid-free status (no intraretinal fluid and no subretinal fluid), and safety.RESULTS: At week 52, brolucizumab was noninferior to aflibercept in BCVA change from baseline (least squares mean difference, -0.6 Early Treatment Diabetic Retinopathy Study letters; 95% confidence interval [CI], -2.1 to 0.9; P < 0.001). A total of 4.8% and 1.7% of participants reported a 15-letter or more BCVA loss from baseline at week 52 in the brolucizumab and aflibercept groups, respectively. In eyes treated with brolucizumab compared with those treated with aflibercept, the CST was reduced significantly (P < 0.001), and a significantly greater proportion of eyes were fluid free at week 52 (40.4% brolucizumab vs. 19.0% aflibercept; 95% CI, 13.9-29.0; P < 0.001). Incidence of intraocular inflammation (IOI), including retinal vasculitis and retinal vascular occlusion, were 9.3% (0.8% and 2.0%) for brolucizumab versus 4.5% (0% and 0%) for aflibercept, respectively.CONCLUSIONS: Visual acuity outcomes in previously treated participants with nAMD and persistent retinal fluid receiving brolucizumab 6 mg dosed every 4 weeks were noninferior to aflibercept 2 mg dosed every 4 weeks, with superior anatomic outcomes. However, incidences of IOI, including retinal vasculitis and retinal vascular occlusion, also were higher, leading to study termination.
KW - BCVA
KW - Brolucizumab
KW - Intraretinal fluid
KW - Subretinal fluid
KW - Receptors, Vascular Endothelial Growth Factor/therapeutic use
KW - Intravitreal Injections
KW - Humans
KW - Neurofibromin 2
KW - Macular Degeneration/drug therapy
KW - Treatment Outcome
KW - Retinal Vasculitis/drug therapy
KW - Wet Macular Degeneration/diagnosis
KW - Antibodies, Monoclonal, Humanized
KW - Recombinant Fusion Proteins/therapeutic use
KW - Angiogenesis Inhibitors/therapeutic use
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U2 - 10.1016/j.ophtha.2022.04.028
DO - 10.1016/j.ophtha.2022.04.028
M3 - Article
C2 - 35537533
AN - SCOPUS:85135933328
SN - 0161-6420
VL - 129
SP - 974
EP - 985
JO - Ophthalmology
JF - Ophthalmology
IS - 9
ER -