To compare the visual acuity of m.11778G>A MT-ND4 Leber hereditary optic neuropathy (LHON) patients treated with lenadogene nolparvovec in clinical studies to the spontaneous evolution of visual acuity in an external control group of m.11778G>A MT-ND4 LHON patients.

A previous analysis was performed on treated patients from three phase 3 studies. This updated analysis incorporates a fourth study, REFLECT, in which patients received lenadogene nolparvovec unilaterally or bilaterally.

Data of 174 MT-ND4 LHON patients intravitreally injected in one or both eyes were pooled from four phase 3 studies: REVERSE, RESCUE, RESTORE and REFLECT. The external control group included 208 age-comparable (> 15 years old) untreated m.11778G>A MT-ND4 LHON patients from 11 natural history studies.

Eyes treated with lenadogene nolparvovec had better visual acuity at all timepoints when compared to natural history eyes. Mean improvement versus natural history was -0.30 LogMAR (+15 letters) at last observation (p<0.01) with a maximal follow-up of 3.9 years after injection. When adjusting for covariates, the mean gain was -0.43 LogMAR (+21.5 letters) (p<0.0001). The size of the treatment effect was larger in patients who received bilateral treatment than in patients who received unilateral treatment.

This comparison of treated patients with natural history patients confirmed a clinically meaningful and sustained improvement in visual acuity induced by lenadogene nolparvovec intravitreal injection in m.11778G>A MT-ND4 LHON patients.