June 2023
Volume 64, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2023
Elamipretide-Mediated Visual Function Improvements Are Associated With Ellipsoid Zone Integrity in Patients With Geographic Atrophy
Author Affiliations & Notes
  • David Lally
    New England Retina Consultants, Springfield, Massachusetts, United States
  • Anthony Abbruscato
    Stealth BioTherapeutics Inc, Needham, Massachusetts, United States
  • Sari Yordi
    Cleveland Clinic Cole Eye Institute, Cleveland, Ohio, United States
  • Hasan Cetin
    Cleveland Clinic Cole Eye Institute, Cleveland, Ohio, United States
  • Victoria Eileen Whitmore
    Cleveland Clinic Cole Eye Institute, Cleveland, Ohio, United States
  • Gagan Kalra
    Cleveland Clinic Cole Eye Institute, Cleveland, Ohio, United States
  • Yavuz Cakir
    Cleveland Clinic Cole Eye Institute, Cleveland, Ohio, United States
  • Conor Anthony McConville
    Cleveland Clinic Cole Eye Institute, Cleveland, Ohio, United States
  • Sunil K Srivastava
    Cleveland Clinic Cole Eye Institute, Cleveland, Ohio, United States
  • Justis P Ehlers
    Cleveland Clinic Cole Eye Institute, Cleveland, Ohio, United States
  • Footnotes
    Commercial Relationships   David Lally Alimera Sciences, Apellis, Annexon Biosciences, EyePoint Pharmaceuticals, Genentech, Iveric bio, Novartis, Code C (Consultant/Contractor), Alimera Sciences, Allergan, Apellis, Novartis, Stealth BioTherapeutics, Code R (Recipient), Apellis, Aldeyra Therapeutics, Annexon Biosciences, Chengdu Kanghong Pharmaceutical Group, Emmes/The MacTel Project, EyePoint Pharmaceuticals, Genentech, Iveric bio, Kodiak Sciences, Neurotech, Novartis, Opthea, Optos, Stealth BioTherapeutics, Code S (non-remunerative); Anthony Abbruscato Stealth BioTherapeutics, Code E (Employment); Sari Yordi None; Hasan Cetin None; Victoria Whitmore None; Gagan Kalra None; Yavuz Cakir None; Conor McConville None; Sunil Srivastava None; Justis Ehlers Adverum, Aerpio, Alcon, Allergan, Genentech/Roche, Novartis, Oxurion, Regeneron, Stealth BioTherapeutics, Iveric bio, RegenxBIO, Allegro, Apellis, Zeiss, Code C (Consultant/Contractor), Adverum, Aerpio, Alcon, Allergan, Genentech/Roche, Novartis, Oxurion, Regeneron, Stealth BioTherapeutics, Iveric bio, Zeiss, Code F (Financial Support)
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science June 2023, Vol.64, 2261. doi:
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      David Lally, Anthony Abbruscato, Sari Yordi, Hasan Cetin, Victoria Eileen Whitmore, Gagan Kalra, Yavuz Cakir, Conor Anthony McConville, Sunil K Srivastava, Justis P Ehlers; Elamipretide-Mediated Visual Function Improvements Are Associated With Ellipsoid Zone Integrity in Patients With Geographic Atrophy. Invest. Ophthalmol. Vis. Sci. 2023;64(8):2261.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : To perform a quantitative assessment of the effect of subcutaneous elamipretide (ELAM) on the ellipsoid zone (EZ) integrity and its relationship with visual function in patients with dry age-related macular degeneration (AMD) and geographic atrophy (GA).

Methods : ReCLAIM-2 was a 48-week, randomized, double-masked, placebo-controlled (n = 59), prospective phase 2 clinical trial that evaluated the mitochondrial protective agent, elamipretide 40 mg once daily (n = 117), in advanced AMD with GA. As part of the prespecified analysis plan, the spectral domain optical coherence tomography (SD-OCT) scans were analyzed using a machine learning–enhanced multilayer retinal segmentation platform to assess EZ integrity and OCT-based GA measurements. The post hoc evaluations included a correlation between the change in low-luminance best-corrected visual acuity (LL-BCVA) and the change in total EZ attenuation and an analysis of the LL-BCVA change with respect to the mean central 1 mm EZ-retinal pigment epithelium (RPE) thickness at baseline.

Results : Compared to placebo (PBO), ELAM was associated with a reduction in the progression of EZ attenuation (in mm2) of partial (15% ELAM vs 34% PBO, P = 0.01) and total EZ attenuation (26% ELAM vs 48% PBO, P = 0.04), and more patients experienced a ≥ 2-line gain in LL-BCVA (14.6% ELAM vs 2.1% PBO, P = 0.04). Low-luminance BCVA change at week 48 correlated with the change in the macular percentage of total EZ attenuation (r = -0.35, P < 0.0001). Furthermore, there was a significant correlation between baseline central 1 mm EZ-RPE thickness and change in LL-BCVA at week 48 (r = 0.26, P = 0.02).

Conclusions : These findings demonstrate correlations between both baseline and changes in measures of EZ integrity and changes in visual function following treatment with ELAM in patients with dry AMD. It also supports EZ attenuation as a surrogate endpoint reasonably likely to predict disease progression and a potential clinical/functional benefit from ELAM in dry AMD. For future studies, enrichment strategies based on photoreceptor viability, rather than GA, are likely to be more relevant to the mechanism of action of ELAM.

This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.

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