Pivotal phase II/III Illuminate trial of sepofarsen for the treatment of CEP290-mediated Leber congenital amaurosis 10 did not meet its primary endpoint of best corrected visual acuity at month 12.

Key findings from the top-line results: At Month 12, the mean change from baseline in BCVA in the 160/80 ug dose group was -0.11 logMAR (p=0.96), in the 80/40 ug group -0.13 logMAR (p=0.97), and in the sham group -0.12 logMAR. P values are treatment group vs. sham, ANCOVA. For secondary endpoints full-field stimulus test (FST) and mobility, there was also no difference between the treated and sham groups in the top-line analysis.

Sepofarsen was observed to be generally well-tolerated. Consistent with the findings observed in the Phase 1/II trial, cataracts, CME, and retinal thinning were observed.

Illuminate, a randomized, sham-controlled trial, enrolled 36 participants aged eight years or older with genetically confirmed LCA10 due to the c.2991+1655A>G (p.Cys998X) mutation in the CEP290 gene, at 14 study sites in 9 countries. Participants were randomized to three equal groups (1:1:1) of the target registration dose sepofarsen (160 ug/80 ug loading dose/maintenance doses), a low dose of sepofarsen for masking (80 ug/40 ug loading dose/maintenance doses), or sham procedure, with sepofarsen administered via intravitreal injection and the sham procedure mimicking an injection with no drug or injection given.