Abstract
Purpose :
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. Roughly half of people with ADOA fail driving standards and up to 46% are registered as legally blind. An estimated 65% to 90% of cases are caused by mutations in the OPA1 gene, most of which lead to haploinsufficiency resulting in 50% OPA1 protein expression and disease manifestation. OPA1 is a dynamin-related GTPase that localizes to the mitochondrial inner membrane and reduced levels precipitate the loss of retinal ganglion cells secondary to mitochondrial dysfunction. Currently there is no approved treatment for people living 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. There are limited prospective data on the natural history of ADOA, which is essential to determine the best outcome measures for treatment trials.
Methods :
FALCON is a multicenter, prospective natural history study of people ages 8 to 60 who have an established clinical diagnosis of ADOA that is caused by a heterozygous OPA1 gene variant. No investigational medications or other treatments will be provided. Patients undergo assessments at baseline, 6 months, 12 months, 18 months, and 24 months. There will be no additional follow-up period.
Results :
FALCON has completed enrollment with 48 patients (16 (8-17 years), 22 (18-40 years), and 10 (41-60 years)) across UK, US, Italy, and Denmark. At baseline, 46% were female and 96% were white. Across all patients, at baseline, mean (SD) LogMAR (25%) was 0.57 (0.335) and visual acuity was 56.75 (16.739). Results will provide a dynamic picture of disease progression in ADOA allowing structural and functional correlations with the causative OPA1 genotype.
Conclusions :
FALCON will provide data to inform us about the natural history of ADOA and to support the development of the antisense oligonucleotide (STK-002) as a potential disease-modifying treatment for patients with ADOA. Stoke plans to initiate a Phase 1 study (OSPREY) of its investigational ASO (STK-002).
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.