Durable vision improvement after a single treatment with antisense oligonucleotide sepofarsen: a case report

Leber congenital amaurosis due to CEP290 ciliopathy is being explored by treatment with the antisense oligonucleotide (AON) sepofarsen. One patient who was part of a larger cohort (ClinicalTrials.gov NCT03140969) was studied for 15 months after a single intravitreal sepofarsen injection. Concordant measures of visual function and retinal structure reached a substantial efficacy peak near 3 months after injection. At 15 months, there was sustained efficacy, even though there was evidence of reduction from peak response. Efficacy kinetics can be explained by the balance of AON-driven new CEP290 protein synthesis and a slow natural rate of CEP290 protein degradation in human foveal cone photoreceptors. Post hoc analyses and follow-up of a patient with Leber congenital amaurosis treated with the antisense oligonucleotide sepofarsen as part of a clinical trial indicates sustained improvement of vision 15 months after receiving a single dose of the drug.
Author(s): Artur V. Cideciyan [sup.1] , Samuel G. Jacobson [sup.1] , Allen C. Ho [sup.2] , Alexandra V. Garafalo [sup.1] , Alejandro J. Roman [sup.1] , Alexander Sumaroka [sup.1] , [...]