Results of Phase 2 ReCLAIM-2 study of elamipretide for dry AMD announced by Stealth BioTherapeutics

Stealth BioTherapeutics Corp. has announced new data from the ReCLAIM-2 study of elamipretide in geographic atrophy (GA) secondary to dry age-related macular degeneration (dry AMD) at the American Society of Retina Specialists Clinical Trials at the Summit meeting held May 21 in Lake Tahoe, Nevada.

In a news release, the company noted that the ReCLAIM-2 prespecified analyses demonstrate that elamipretide ameliorated progressive decline, or attenuation, of the mitochondrial rich ellipsoid zone (EZ) layer of the photoreceptors (P < 0.01) and showed a categorical >2-line improvement in low luminance visual acuity (LLVA) (P = 0.04) in patients with GA. Progressive LLVA dysfunction, which is among the first symptoms of dry AMD, compromises patients' ability to see under low-light conditions such as at dusk, in the evening, or indoors using artificial light.

Additional analyses show that, consistent with prior findings from the ReCLAIM Phase 1 study, changes in LLVA correlated with baseline EZ attenuation in ReCLAIM-2. The new analyses also show that elamipretide-mediated reduction of progressive EZ attenuation correlated with improvements in LLVA. Although the trial's primary endpoints of mean change in LLVA and GA progression were not met, these analyses were found to be promising and to support and inform the continued development of elamipretide for dry AMD.

According to the company, dry AMD is a progressive retinal disease in which the photoreceptors, which are specialized neurons found in the retina that convert light into electrical signals required for normal visual function, suffer progressive damage and death, leading to progressive loss of vision. One of the earliest signs of photoreceptor dysfunction is progressive damage to, or attenuation of, the ellipsoid zone (EZ), which is a mitochondrial rich layer of the photoreceptors. EZ attenuation has been shown to precede and predict visual dysfunction in dry AMD and other retinal diseases.

"Preserving the health of structures in the eye needed for visual function, such as photoreceptors, is critical for patients with dry AMD," said Jeffrey Heier, MD, the principal investigator of the ReCLAIM-2 study and director, retina service, and director, retinal research, Ophthalmic Consultants of Boston. "I am pleased to present these data underscoring for the first time the important relationship between mitochondrial health and vision in GA, which we hope will inform future efforts to improve outcomes for patients living with this progressive and irreversible disease."

Elamipretide was generally well tolerated in ReCLAIM-2. The rate of new-onset exudations was 5.3% in the elamipretide treated group versus 6.9% in placebo.

"We are excited to confirm that targeting mitochondrial dysfunction in dry AMD may preserve and potentially improve visual function for some affected patients," Reenie McCarthy, CEO of Stealth BioTherapeutics, said in the news release. "We believe these data can help enrich and inform future development efforts for this devastating disease, and we are evaluating strategies to progress this program, including through potential partnering discussions."

The company is also progressing the clinical development of elamipretide in several rare disease indications as well as advancing a broad pipeline of novel mitochondria-targeting compounds.