Abstract
Purpose :
We previously reported unexpectedly long durability of vision improvement in one eye of a patient with CEP290-associated LCA after a single injection of sepofarsen, an antisense oligonucleotide designed for the deep intronic c.2991+1655A>G mutation (Cideciyan et al., Nat Med 2021). We now evaluate: (1) durability of efficacy beyond 15 months in the previously treated left eye (LE1); (2) peak efficacy and durability after a single injection in the treatment-naive right eye (RE1); and, (3) reattainment of the peak efficacy in the left eye re-injected 4 years after the first injection (LE2).
Methods :
CEP290-LCA patient P11 was followed for 4.2 years. Left eye received a single injection at age 14, right eye received a single injection at age 15, left eye was re-injected at age 18 years. All three intravitreal injections were 160 ug of sepofarsen. Visual function was evaluated with best corrected standard and low-luminance visual acuities (BCVA, LLVA), microperimetry (MP1), dark-adapted chromatic perimetry (DACP), and dark-adapted full-field sensitivity testing (FST). Retinal structure was evaluated with near-infrared-excited autofluorescence (NIR-AF) and OCT imaging.
Results :
Peak efficacy results were measured 3-6 months post injection and reported as log10 change from baseline (CFB) in triplicates referring to LE1, RE1, and LE2, respectively. Negative values are improvements. Peak CFBs were: -0.09, -0.11, -0.14 logMAR for BCVA; -0.34, -0.36, -0.26 logMAR for LLVA; -1.24, -0.94, -0.46 log for MP1 at fovea; -0.75, -1.01, -0.82 log for DACP at fovea; -0.75, -0.91, -0.60 log for FST. Long term data were available for LE1 and RE1. All visual function measures showed tendency for stability or slow reduction from peak with BCVA, LLVA, MP1, DACP, and FST remaining on average -0.09, -0.19, -0.62, -0.37, and -0.54 log, respectively, better than baseline at ~2 years after each single injection. Near-baseline values were reached 3-4 years post injection for most measures. The horizontal and vertical extents of centrally retained elliptical region of melanization on NIR-AF did not change significantly for either eye over the duration of the study. Quantification of OCT parameters are ongoing.
Conclusions :
Significant, reproducible and clinically meaningful improvements of vision are durable to at least 2 years following each single injection of sepofarsen.
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.