Congress Posters
Sepofarsen is an RNA therapy targeting the c.2991+1655A>G mutation in CEP290 that causes Leber’s Congenital Amaurosis type 10 (LCA10). The study aimed at understanding the inconsistencies observed in the results from a previously conducted clinical study and whether a change of study design to a paired-eye paradigm (i.e., comparing eyes with and without treatment within the same patient) in a clinical study would be better. Visual acuity, or eye chart improvements of approximately 8 letters gain on a standard eye chart were seen after 12 months of treatment when the two eyes were compared to each other in 15 individuals included in the analysis. In general, reduced variability (less noise in measurement) was observed across the two eyes in visual function assessments. These results showed that comparing eyes of a clinical trial participant in a study in this rare disease is a better way of identifying treatment response of sepofarsen in LCA10 patients.
This abstract explains the use of the Freiburg Vision Test (FrACT) in individuals with low vision or ultra-low vision due to Leber Congenital Amaurosis Type 10 (LCA10), in comparison to standard vision testing using the eye chart. Many individuals with ultra-low vision are unable to read the standard eye chart. The FrACT test was reviewed throughout the ILLUMINATE clinical trial of sepofarsen in a limited number of individuals with LCA10 to understand its use as a clinical test. FrACT test results were compared to the standard eye chart results. The analysis showed consistency between FrACT and the standard eye chart measure and showed better accuracy when repeated. Repeatability is important in clinical test analysis. Therefore, the FrACT test appears to be a good clinical test to assess vision in individuals and future clinical trial participants with ultra-low vision.
Mutations (“alterations”) in the USH2A gene disrupt the production of an important protein called usherin, causing photoreceptor death, affecting vision function and ultimately leading to vision loss. They are among the most common causes of retinitis pigmentosa (RP) but no treatments exist for this condition. Ultevursen, an mRNA medicine in clinical trials, is designed to overcome a genetic defect in the exon 13 mutation in the USH2A gene and aims to restore this important protein. This may slow or stop some effects of RP. Safety results of 29 individuals who received at least one dose of ultevursen and were followed for 72 to 1288 days showed ultevursen to be well tolerated with no serious adverse events. Effectiveness of ultevursen was also measured in the STELLAR clinical study, which showed measurable trends towards stabilization of visual function and visual field as well as preservation of photoreceptors, showing that retinal structure could be a good future measure for disease progression and intervention by ultevursen. Data from STELLAR was compared with the RUSH2A natural history study and showed that RUSH2A may be a suitable natural history comparator for the ultevursen clinical trials.