Stealth BioTherapeutics Starts Global Phase 3 Trial for Elamipretide in Dry AMD

Stealth BioTherapeutics, a clinical-stage biopharmaceutical company based in Needham, Massachusetts, has announced a significant milestone in its Phase 3 clinical program for elamipretide, a treatment targeting dry age-related macular degeneration (dry AMD). The company recently enrolled and administered the first dose to a patient in its ReNEW trial (NCT06373731). This trial, along with ReGAIN, constitutes the Phase 3 program designed to evaluate the efficacy, safety, and pharmacokinetics of elamipretide administered via daily subcutaneous injections in individuals with dry AMD.

The primary focus of these trials is to measure the progression rate of photoreceptor loss in the macular area, using spectral domain-optical coherence tomography (SD-OCT) and ellipsoid zone (EZ) mapping over a period of 48 weeks. Reenie McCarthy, Chief Executive Officer of Stealth BioTherapeutics, emphasized the importance of this development, stating that enrolling the first patient brings the company closer to providing a potentially groundbreaking home treatment for dry AMD sufferers. She noted that with multiple active sites in the United States, the trials are off to a promising start.

Dr. Charles Wykoff from Retinal Consultants of Texas highlighted the critical need for new therapeutic options with unique mechanisms to manage dry AMD, particularly treatments that can be easily administered in the early stages of the disease. Dr. Wykoff pointed out that elamipretide, which targets mitochondrial dysfunction, offers a novel approach by addressing the underlying bioenergetic imbalances responsible for the progressive loss of photoreceptors and subsequent visual decline characteristic of AMD.

The ReNEW and ReGAIN trials aim to rigorously evaluate the daily use of elamipretide in combating dry AMD. In the ReNEW trial, 360 participants will be randomized in a 2:1 ratio to receive either elamipretide or a placebo over a 96-week period, with an option to join an open-label extension trial known as ReTAIN.

Dry AMD is a significant cause of irreversible blindness, affecting an estimated 19.8 million Americans aged 40 and older, with 85% to 90% of cases being classified as dry AMD. This progressive retinal disease involves the gradual damage and death of photoreceptors, specialized neurons in the retina that convert light into electrical signals necessary for vision. Several factors, including aging, smoking, obesity, and cardiovascular health, are linked to mitochondrial dysfunction, which precedes the clinical symptoms of AMD and worsens as the disease progresses. Photoreceptor loss can be gauged through measurements of the thickness between the EZ and retinal pigment epithelium (EZ-RPE thickness), a marker that often predicts the decline in visual function and the onset of geographic atrophy in dry AMD.

Stealth BioTherapeutics is committed to developing innovative therapies for age-related and rare genetic diseases tied to mitochondrial dysfunction. The company’s leading candidate, elamipretide, is currently in Phase 3 trials for dry AMD and primary mitochondrial myopathy, and is under review by the FDA for Barth syndrome, a rare cardioskeletal disease. Additionally, Stealth is developing a second-generation candidate, bevemipretide (SBT-272), for eye and neurological conditions, and has a robust pipeline of mitochondria-targeted compounds under investigation.