ONL Therapeutics has achieved a significant milestone in its development of xelafaslatide, announcing the randomization of the first patient in its global Phase 2 GALAXY trial. The study evaluates this investigational first-in-class small molecule Fas inhibitor in patients with geographic atrophy (GA) associated with dry age-related macular degeneration (AMD).
Xelafaslatide, formerly known as ONL1204, recently received approval from the World Health Organization and United States Adopted Names Council for its nonproprietary name. The compound is designed to protect key retinal cells, including photoreceptors, from cell death that occurs across a range of retinal diseases and conditions.
Novel Mechanism Addresses Unmet Medical Need
"GA remains a devastating condition with a high unmet need," said Dr. David R.P. Almeida, executive chairman of Erie Retina Research in Erie, Pennsylvania. "With its novel therapeutic pathway targeting Fas, and dosing every three to six months, xelafaslatide has the potential to make a significant positive impact for patients while also lowering the treatment burden associated with currently approved GA therapies."
The Fas pathway represents a critical mechanism in retinal cell death, with death of these cells through both direct and inflammatory signaling pathways being the root cause of vision loss and a leading cause of blindness.
Phase 2 GALAXY Trial Design
The GALAXY trial (NCT06659445) will enroll approximately 324 patients across sites in the United States, Canada, and the European Union. The study design includes three experimental arms featuring two dose levels and two treatment frequencies, with xelafaslatide administered via intravitreal injection every 12 weeks or every 24 weeks.
The primary endpoint focuses on the rate of growth of the GA lesion area in patients treated with xelafaslatide versus sham, as assessed by fundus autofluorescence (FAF) measured at 48 weeks. Additional timepoints will extend measurements to 72 weeks, and an active reference arm will be available to patients at US sites only.
Building on Promising Early Data
The Phase 2 trial builds upon encouraging results from a Phase 1b study that demonstrated xelafaslatide to be generally safe and well tolerated, with efficacy signals observed after six months. The Phase 1b study enrolled 28 patients in Australia and New Zealand, following participants for 24 weeks to assess lesion growth rates before randomization to receive either low dose (50 micrograms), high dose (200 micrograms), or sham injection.
"The continued support of the retina specialist community for the GALAXY trial underscores the strong interest in xelafaslatide and its unique and differentiated mechanism of action targeting Fas," said David N. Zacks, chief scientific officer of ONL Therapeutics. "We are committed to advancing xelafaslatide as a potential breakthrough neuroprotection therapy for GA to help clinicians address the needs of patients facing this progressive, vision-threatening disease."
Broader Development Program
ONL Therapeutics' clinical development program for xelafaslatide extends beyond GA treatment. The company has completed a Phase 2 study in the United States for macula-off retinal detachment, a condition for which the compound has received orphan drug designation from the FDA. Additional completed studies include Phase 1b trials in patients with progressing open-angle glaucoma and a Phase 1 trial in macula-off retinal detachment patients in Australia and New Zealand.
Disease Context
AMD has emerged as a major cause of visual disability and legal blindness globally. While generally affecting only the central retina (macula), this region provides the visual acuity necessary for reading, driving, and performing fine vision-related tasks. Associated with aging, cigarette smoking, obesity, nutrient-deficient diets, cardiac risk-related lifestyle factors, and genetic components, AMD represents an increasingly prevalent public health concern as the global population ages. GA, also called atrophic AMD, represents an advanced form of this condition.
