Stoke Therapeutics Presents 2-Year Data from FALCON Study in Autosomal Dominant Optic Atrophy
Stoke Therapeutics announced 2-year results from the FALCON study, a prospective natural history study in people with the inherited optic nerve disorder Autosomal Dominant Optic Atrophy (ADOA) (n=47). The data have informed the company’s clinical development program for the proprietary antisense oligonucleotide (ASO) STK-002, currently being evaluated in the phase 1 OSPREY study.
The findings were presented at the 2025 American Academy of Ophthalmology (AAO) Annual Meeting in Orlando.
The FALCON study, conducted across 10 international sites in the United States, United Kingdom, Italy, and Denmark, followed patients with ADOA for 24 months to better understand disease progression and identify meaningful endpoints for clinical trials. The study revealed several key findings:
Slow but measurable vision loss: While ADOA caused by OPA1 gene mutations generally progresses slowly, 24% of patients experienced a loss of at least five letters in low-contrast visual acuity (LCVA), a sensitive measure of early optic nerve dysfunction.
Mitochondrial dysfunction: Patients with ADOA demonstrated higher levels of mitochondrial impairment than healthy individuals. Because mitochondria supply most of the energy to the optic nerve, these findings highlight the crucial role of mitochondrial health in visual preservation.
Potential for reversibility: No significant anatomical retinal changes were observed over the study period, suggesting that functional retinal impairment may be reversible if treated early.
“These findings suggest that impaired function in the retina and optic nerve occurs before permanent cell loss,” said Patrick Yu-Wai-Man, MD, PhD, Professor of Ophthalmology at the University of Cambridge, Moorfields Eye Hospital, and UCL Institute of Ophthalmology, and principal investigator of the ongoing OSPREY phase 1 study. “By increasing naturally occurring OPA1 protein to improve mitochondrial function, it may be possible to stabilize and even restore vision in people with ADOA. The FALCON study also provides promising measures of disease progression that can guide future interventional studies.”
With 47 patients aged 8–60 years, FALCON represents the largest prospective, multicenter natural history study conducted in ADOA to date, according to Stoke. Participants, all with genetically confirmed OPA1 variants, underwent serial assessments every 6 months over 2 years. No investigational therapy was administered, allowing for a clear view of untreated disease progression.
Study Presentation at AAO 2025
Presentation Details
Title: FALCON Natural History Study: Longitudinal Assessment of Functional and Anatomical Changes in OPA1 Autosomal Dominant Optic Atrophy
Presenter: Dr. Patrick Yu-Wai-Man, M.D., Ph.D.
Session: Podium Poster, PT01
Date/Time: Saturday, October 18, 9:15–10:15 a.m. ET
Location: Poster Theater, Hall WB4, Orange County Convention Center, Orlando, FL
ADOA is the most common inherited optic nerve disorder. It is a rare disease that causes progressive and irreversible vision loss in both eyes starting in the first decade of life. Severity can vary and the rate of vision loss can be difficult to predict. Roughly half of people with ADOA fail driving standards and up to 46% are registered as legally blind. More than 400 different OPA1 variants have been reported in people diagnosed with ADOA. ADOA affects approximately one in 30,000 people globally with a higher incidence in Denmark of one in 10,000 due to a founder effect. Currently there is no approved treatment for people living with ADOA.