ASRS 2022 – Elamipretide for Noncentral Geographic Atrophy

Theo Bowe, MD
Wills Eye Hospital

Dr. Jeffrey Heier from Ophthalmic Consultants of Boston presented the ReCLAIM-2 trial, a phase 2 trial of elamipretide in patients with non-central geographic atrophy (GA). Elamipretide is a small tetrapeptide which localizes to mitochondria, stabilizes cardiolipin, and reduces the production of toxic reactive oxygen species.

Progressive mitochondrial dysfunction contributes to age-related macular degeneration with decreases in mitochondria per cell and cristae per mitochondria. Cardiolipin promotes inner mitochondrial curvature which helps to organize respiratory complexes, and thus supports the reduction in pathologic reactive oxygen species.

In the ReCLAIM-2 trial, elamipretide was administered subcutaneously. Patients were randomized between elamipretide and control in a 2:1 ratio. The inclusion criteria comprised eyes with non-central (at least 150 microns from the foveal center) GA lesions ranging in size from 0.5mm to 10mm.

The primary endpoint was mean change in low luminance best corrected visual acuity (LL BCVA) and change in the size of geographic atrophy lesions. Secondary outcomes included categorical change in LL BCVA and ellipsoid zone (EZ) attenuation.

Baseline characteristics were well matched between the intervention and control arms, other than baseline LL BCVA and EZ attenuation, both of which may have disfavored elamipretide. The safety profile was consistent with prior studies. Adverse events were primarily related to injection site complications.

ReCLAIM-2 did not meet either of its two primary endpoints. However, Dr. Heier pointed out that this phase 2 study succeeded in giving further information about the risks and benefits of elamipretide and provided insights into the design of subsequent studies.

EZ damage can precede vision loss and precede GA in AMD. ReCLAIM-2 demonstrated that elamipretide reduced attenuation of the EZ, which correlates with visual function improvement. There was a two line improvement in LL BCVA in the elamipretide arm. These findings support further investigation of elamipretide in the treatment of GA and other diseases with EZ attenuation and mitochondrial dysfunction.