Stealth BioTherapeutics Inc. has reached the halfway mark in patient recruitment for its global Phase 3 ReNEW clinical trial, enrolling 180 of the targeted 360 participants to evaluate elamipretide as a potential treatment for dry age-related macular degeneration (dry AMD).
The ReNEW study (NCT06373731) is testing daily subcutaneous injections of elamipretide, a first-in-class mitochondria-targeted investigational therapeutic, in patients with dry AMD. The primary efficacy endpoint, agreed upon with the FDA, will measure the rate of change in the macular area of photoreceptor loss, assessed using spectral domain-optical coherence tomography (SD-OCT) and ellipsoid zone (EZ) mapping.
"Dry AMD, and its late-stage manifestation geographic atrophy, is a devastating disease process that leads to progressive visual dysfunction and irreversible vision loss. Our patients are in need of new and improved treatment options," said Charles Wykoff, MD, PhD from Retinal Consultants of Texas, and Chair of Stealth's ReNEW Trial Scientific Review Committee.
Dr. Wykoff highlighted that progressive thinning of photoreceptors—specialized light-detecting cells in the retina that enable vision in both bright and dim light conditions—is a consistent and early hallmark of dry AMD. Loss of these cells is closely associated with worsening visual function.
Novel Mechanism Targeting Mitochondrial Dysfunction
Elamipretide represents a new approach to treating dry AMD by targeting mitochondrial dysfunction, which has been associated with aging, smoking, obesity, and cardiovascular health. Research indicates that mitochondrial dysfunction precedes clinical symptoms of AMD and increases as the disease progresses.
"The rapid enrollment of the pivotal Phase 3 ReNEW study underscores this community's desire for novel therapeutics that can be self-administered at home and offer the potential to improve visual function," said Reenie McCarthy, Chief Executive Officer of Stealth. "By targeting retinal bioenergetics to reduce the loss of photoreceptors, we hope to disrupt the progressive vision loss that characterizes this devastating disease."
Clinical Trial Design and Timeline
The ReNEW trial design includes randomization of patients in a 2:1 ratio to either elamipretide or placebo for 96 weeks, with an option for participants to enroll in an open-label extension trial called ReTAIN. The primary endpoint will be assessed at week 48.
In addition to the ReNEW study, Stealth plans to initiate a second global Phase 3 trial in dry AMD called ReGAIN in the coming months. Data from the ReNEW study is expected to be reported in 2026.
Significant Unmet Medical Need
AMD is the leading cause of irreversible blindness, affecting an estimated 19.8 million Americans aged 40 and older according to the Vision and Eye Health Surveillance System. Dry AMD accounts for 85% to 90% of all AMD cases.
The disease is characterized by progressive damage and death of photoreceptors, specialized neurons in the retina that convert light into electrical signals required for normal visual function. This damage leads to loss of vision that currently has limited treatment options.
Photoreceptor loss can be quantified by measuring the thickness between the ellipsoid zone and retinal pigment epithelium. Loss of photoreceptor cells, or EZ attenuation, has been shown to precede and predict the loss of visual function and areas of geographic atrophy in dry AMD.
Expanding Pipeline for Mitochondrial Diseases
Stealth BioTherapeutics is also evaluating elamipretide in other indications. The company is conducting a fully enrolled Phase 3 clinical trial in primary mitochondrial myopathy, a rare skeletal myopathic disease. Additionally, elamipretide is under review by the Food and Drug Administration for Barth syndrome, an ultra-rare cardioskeletal disease.
The company is also developing bevemipretide (SBT-272), its second-generation clinical-stage candidate, for ophthalmic and neurological disease indications, as part of its pipeline of novel mitochondria-targeted compounds.
The successful completion of the ReNEW and planned ReGAIN trials could potentially provide a new therapeutic option for millions of patients suffering from dry AMD, offering a home-based treatment that addresses the underlying mitochondrial dysfunction associated with this devastating disease.
