Purpose
Design
Participants
Methods
Main Outcome Measures
Results
Conclusions
Keywords
Abbreviations and Acronyms:
AE (adverse event), CFP (color fundus photography), FA (fluorescein angiography), ETDRS (Early Treatment Diabetic Retinopathy Study), IOI (intraocular inflammation), MedDRA (Medical Dictionary for Regulatory Activities), nAMD (neovascular age-related macular degeneration), SRC (Safety Review Committee), VEGF (vascular endothelial growth factor)BEOVU®(brolucizumab-dbll) injection, for intravitreal use. US Prescribing Information. 2020.
BEOVU®(brolucizumab-dbll) injection, for intravitreal use. US Prescribing Information. 2020.
Methods
Role of the SRC
Source Data
Review Process
Outcomes
Statistical Analysis
Results
Analysis Population (Brolucizumab-Treated Eyes)
Incidence of Definite/Probable IOI, Retinal Vasculitis, and Retinal Vascular Occlusion Events (Brolucizumab-Treated Eyes)

Risk of Visual Acuity Loss Associated with IOI ± Retinal Vasculitis ± Retinal Vascular Occlusion Events
Visual Acuity Loss Event | No. of Cases | Incidence in HAWK and HARRIER | Incidence in Subgroup with Event | ||
---|---|---|---|---|---|
n/N | % | n/N | % | ||
Visual acuity loss, cases with IOI | |||||
At least moderate | 8 | 8/1088 | 0.74% | 8/50 | 16.0% |
Severe | 5 | 5/1088 | 0.46% | 5/50 | 10.0% |
Visual acuity loss, cases with IOI without retinal vasculitis | |||||
At least moderate | 0 | 0/1088 | 0.0% | 0/14 | 0.0% |
Severe | 0 | 0/1088 | 0.0% | 0/14 | 0.0% |
Visual acuity loss, cases with IOI + retinal vasculitis | |||||
At least moderate | 8 | 8/1088 | 0.74% | 8/36 | 22.2% |
Severe | 5 | 5/1088 | 0.46% | 5/36 | 13.9% |
Visual acuity loss, cases with IOI + retinal vasculitis without retinal occlusion | |||||
At least moderate | 1 | 1/1088 | 0.09% | 1/13 | 7.69% |
Severe | 0 | 0/1088 | 0.0% | 0/13 | 0.0% |
Visual acuity loss, cases with IOI + retinal vasculitis + retinal occlusion | |||||
At least moderate | 7 | 7/1088 | 0.64% | 7/23 | 30.4% |
Severe | 5 | 5/1088 | 0.46% | 5/23 | 21.7% |
Timing of Definite/Probable IOI, Retinal Vasculitis, and Retinal Vascular Occlusion and Visual Acuity Loss Events (Brolucizumab-Treated Eyes)



Analysis of Eyes Treated with Aflibercept
Overall Loss of Visual Acuity in the HAWK and HARRIER Studies
Discussion
- Do D.
BEOVU®(brolucizumab-dbll) injection, for intravitreal use. US Prescribing Information. 2020.
Acknowledgments
Supplementary Data
- Table S1
- Figure S1
References
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Article Info
Publication History
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In Press Journal Pre-ProofFootnotes
Supplemental material available at www.aaojournal.org.
Disclosure(s): All authors have completed and submitted the ICMJE disclosures form.
The author(s) have made the following disclosure(s): C.P.: Personal fees – Novartis PHARMA, other from Novartis Pharma, during the conduct of the study; Personal fees and other – Bayer Pharma, Novartis Pharma, Roche Pharma, outside the submitted work.
J.S.H.: Personal fees – 4DMT, Adverum, Aerie, Aerpio, Aldeyra, Allegro, Alzheon, Annexon, Apellis, Asclepix, Aviceda, Beaver-Visitec, DTx, Eloxx, Galimedix, Genentech, Gyroscope, iRenix, jCyte, Kala, Kanghong, NGM, Notal Vision, Novartis, Ocugenix, Oculis, Ocunexus, Ocular Therapeutix, Oxurion, Palatin, Pfizer, Regeneron, Regenxbio, Santen, Scifluor, Shire, Stealth, Thea, Tyrogenex, Vinci, Voyant; Grants – Aerie, Aerpio, Apellis, Genentech, Graybug, Gyroscope, Hemera, Janssen R&D, KalVista, Kanghong, Novartis, Ophthotech, Optovue, Regeneron, Regenxbio, Stealth, outside the submitted work.
I.K.K.: Personal fees – Novartis, during the conduct of the study; Personal fees – Kodiak Sciences; Nonfinancial support – Allergan; Personal fees – Biophytis and Castle Biosciences, outside the submitted work.
J.M.: Grants and personal fees – Novartis, Alcon, Roche, Bayer, Apellis, Kodiak Sciences, Reneuron, Genentech; Grants, Personal fees, and other – Iveric Bio; Personal fees - Cellcure, Lineage Cell Therapeutics, Maculogix; Personal fees and other – Notal Vision; outside the submitted work.
F.H.: Novartis; during the conduct of the study; Apellis, Heidelberg Engineering, Zeiss, Acucela, Genentech/Roche, Allergan, Boehringer-Ingelheim, Bayer Healthcare, LIN Bioscience, Pixium, Kanghorn, Oxurion, Grayburg Vision, Stealth BioTherapeutics, Geuder; outside the submitted work.
J.F.K.: Personal fees – Bayer, Novartis, Kanghong, Roche, Allergan, Thea; outside the submitted work. R.T.: Personal fees – Novartis, during the conduct of the study; Grants and personal fees – Novartis, Bayer; Personal fees – Alcon; Nonfinancial support – Zeiss; Personal fees –Genentech, Roche, Allergan, Thea, Oculis, outside the submitted work.
T.M.: no relevant conflicts. S.K.S.: Personal fees – Novartis, during the conduct of the study; Grants and personal fees – Novartis, Regeneron; Personal fees – Zeiss; Grants and personal fees – Bausch + Lomb, Eyepoint; Personal fees – Clearside; Grants – Santen; Personal fees – RegenerxBio, from null, outside the submitted work.
G.J.J.: Personal fees – Novartis, during the conduct of the study; Personal fees – Novartis, Iveric, Regeneron, EyePoint, outside the submitted work.
T.A.A.: Personal fees – Novartis, during the conduct of the study; Personal fees – Novartis, outside the submitted work.
P.K.K.: Personal fees – Bayer, Regeneron, Allergan, Novartis; Nonfinancial support – Carl Zeiss Meditec; Personal fees – Kanghong, Kodiak, Formycon/BioEq, outside the submitted work.
Novartis Pharma AG funded the original phase 3 HAWK and HARRIER clinical trials, the expenses of the SRC analysis, and the medical writing support for this manuscript. The autonomy of the SRC was established upfront via a charter; as such, the SRC selected the cases and data to review, completed the analysis and assessment of relevant reports, and agreed as a group the conclusions reported. Novartis did not influence the findings and was not involved in the development of this manuscript. Novartis completed quality checks of the manuscript for accuracy but did not recommend any material changes to the content. All authors provided full approval of the final manuscript as submitted to Ophthalmology.
Selected data have been published via brolucizumab.info and made available to relevant societies, including the Macula Society, American Academy of Ophthalmology, American Society of Retina Specialists, Retina Society, Japanese Retina Vitreous Society, and EURETINA.
HUMAN SUBJECTS: Human subjects were included in this post hoc analysis. Protocols were approved by an Independent Ethics Committee/Institutional Review Board. All research adhered to the tenets of the Declaration of Helsinki. All participants provided informed consent.
No animal subjects were used in this study.
Author Contributions:
Conception and design: Monés, Srivastava, Jaffe, Tadayoni, Albini, Kaiser, Holz, Korobelnik, Kim, Pruente, Murray, Heier
Data collection: Monés, Srivastava, Jaffe, Tadayoni, Albini, Kaiser, Holz, Korobelnik, Kim, Pruente, Murray, Heier
Analysis and interpretation: Monés, Srivastava, Jaffe, Tadayoni, Albini, Kaiser, Holz, Korobelnik, Kim, Pruente, Murray, Heier
Obtained funding: N/A
Overall responsibility: Monés, Srivastava, Jaffe, Tadayoni, Albini, Kaiser, Holz, Korobelnik, Kim, Pruente, Murray, Heier
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