Purpose : LCA10 is a severe, degenerative inherited retinal disease resulting in childhood blindness, which has no treatment. Sepofarsen is an intravitreal RNA antisense oligonucleotide which showed clinically meaningful results following unilateral injection in a Ph1b/2 trial for LCA10 due to the c.2991+1655A>G mutation in the CEP290 gene. Safety and efficacy of sepofarsen dosed in the second eye was evaluated in the extension trial (Insight; NCT03913130).
Methods : Patients who completed the Ph1b/2 trial, multicenter, open-label, multiple-dose escalation sepofarsen trial were given the opportunity to enroll into the extension trial for continued dosing in their first treated eye as well as initiation of treatment in their second eye with the 160/80µg loading/maintenance dose, using a 6-monthly dosing interval. Nine out of 11 patients from the Ph1b/2 trial enrolled in the extension trial. As main efficacy parameters, change in Best-Corrected Visual Acuity (BCVA) and Full-Field Stimulus Test (FST) were assessed.
Results : At data cut-off in July 2020, 4 patients aged 15–45 years had received 1 intravitreal injection of sepofarsen in their second eye and had completed a 3- or 6-month visit. One patient developed cataract at Month 9 in the second treated eye. No other safety findings were reported. Meaningful BCVA improvements (>-0.8 logMAR) were reported in the second treated eye for 2 of the 4 patients, similar to the improvements observed in their first treated eye. All 4 patients showed a FST improvement ranging from -0.74 to -2.35 log cd/m2, generally similar to the FST responses observed in their first treated eyes.
Conclusions : This data analysis strongly corroborates the clinically meaningful vision improvements and safety profile observed in the Ph1b/2 trial. Second eye responses to sepofarsen parallel the first eye treated responses both in visual acuity and retinal sensitivity (FST) improvements. Sepofarsen safety profile for the 160/80µg dose group in this extension trial is consistent with that observed in the Ph1b/2 trial. Further analyses on this ongoing extension trial and the Ph2/3 trial (Illuminate; NCT03913143) are expected