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Case Reports
. 2024 Sep 19;13(18):5540.
doi: 10.3390/jcm13185540.

Multifocal Electroretinography Changes after UBX1325 (Foselutoclax) Treatment in Neovascular Age-Related Macular Degeneration

Nathan Macha  1   2 , Minzhong Yu  3 , Przemyslaw Sapieha  4 , Sharon Klier  5 , Anirvan Ghosh  5 , Lorraine White  2 , Raj K Maturi  1   2
Affiliations
Case Reports

Multifocal Electroretinography Changes after UBX1325 (Foselutoclax) Treatment in Neovascular Age-Related Macular Degeneration

Nathan Macha et al. J Clin Med. .

Abstract

Background/Objectives: The objective of this study was to determine the treatment effect of foselutoclax in neovascular age-related macular degeneration (AMD) by multifocal electroretinography (mfERG) and evaluate mfERG as a potential clinical endpoint in AMD studies. Methods: A total of five subjects were included in the study who had active choroidal neovascularization and a history of at least two anti-vascular endothelial growth factor (VEGF) injections in the last 6 months. Subjects received a 50 µL intravitreal injection of foselutoclax at the baseline visit and Weeks 4, 24, and 28 of the study period. Results: After foselutoclax treatment, the largest improvement in the mfERG N1-P1 response density occurred at Week 8 as three of five subjects achieved a ≥20% gain. In addition, three of five subjects demonstrated a BCVA improvement of ≥5 ETDRS letters over baseline at Weeks 4, 8, and 24. The mean change in BCVA demonstrated statistical significance in Weeks 4 and 8, showing increases of 5 (p = 0.02) and 6.2 (p = 0.02) letters, respectively. Conclusions: Foselutoclax treatment was shown to have the potential to recover outer retinal function as determined by mfERG and BCVA at approximately Week 8 of treatment.

Keywords: anti-VEGF; multifocal electroretinography; neovascular age-related macular degeneration; senescence.

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Conflict of interest statement

Sharon Klier and Anirvan Ghosh are employees of UNITY Biotechnology. Raj Maturi was an investigator in the Phase 2 ENVISION study and is a consultant for UNITY Biotechnology.

Figures

Figure 1
Figure 1
(a) Percentage change from baseline in the total N1-P1 response density and (b) changes from baseline in BCVA at each visit of all study eyes. Subject 001 was unable to undergo testing at Weeks 36 and 48. Subjects 003 and 004 both received rescue aflibercept treatments at Weeks 24 and 36.
Figure 1
Figure 1
(a) Percentage change from baseline in the total N1-P1 response density and (b) changes from baseline in BCVA at each visit of all study eyes. Subject 001 was unable to undergo testing at Weeks 36 and 48. Subjects 003 and 004 both received rescue aflibercept treatments at Weeks 24 and 36.
Figure 2
Figure 2
Testing results of Subject 010, including (a) mfERG trace arrays at each visit, (b) mfERG 3D topographical distributions at each visit, and (c) baseline OCT retinal thickness heat map overlayed on fundus imaging. In trace arrays, green circles indicate regions of increased N1-P1 response densities from baseline, and red circles indicate regions of decreased N1-P1 response densities from baseline. mfERG plots show the response density increases to the maximum at Week 8 and reduces from Weeks 24 to 48.
Figure 2
Figure 2
Testing results of Subject 010, including (a) mfERG trace arrays at each visit, (b) mfERG 3D topographical distributions at each visit, and (c) baseline OCT retinal thickness heat map overlayed on fundus imaging. In trace arrays, green circles indicate regions of increased N1-P1 response densities from baseline, and red circles indicate regions of decreased N1-P1 response densities from baseline. mfERG plots show the response density increases to the maximum at Week 8 and reduces from Weeks 24 to 48.
Figure 3
Figure 3
Testing results of Subject 003, including (a) mfERG trace arrays at each visit, (b) mfERG 3D topographical distributions at each visit, and (c) baseline OCT retinal thickness heat map overlayed on fundus imaging. In trace arrays, green circles indicate regions of increased N1-P1 response densities from baseline, and red circles indicate regions of decreased N1-P1 response densities from baseline. If an individual waveform was identified as noise, it was excluded from assessment for fluctuations in amplitude. mfERG plots show the response densities increase to the maximum at Week 8 and reduce from Weeks 24 to 48.
Figure 3
Figure 3
Testing results of Subject 003, including (a) mfERG trace arrays at each visit, (b) mfERG 3D topographical distributions at each visit, and (c) baseline OCT retinal thickness heat map overlayed on fundus imaging. In trace arrays, green circles indicate regions of increased N1-P1 response densities from baseline, and red circles indicate regions of decreased N1-P1 response densities from baseline. If an individual waveform was identified as noise, it was excluded from assessment for fluctuations in amplitude. mfERG plots show the response densities increase to the maximum at Week 8 and reduce from Weeks 24 to 48.
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