Objective:

To provide efficacy and safety data on the use of lenadogene nolparvovec gene therapy (LNGT) in real-life conditions in patients with Leber hereditary optic neuropathy (LHON) caused by the m.11778G>A ND4 variant.

Background:

Early access programs (EAP) allowed patients with ND4-LHON to benefit from LNGT, which is not yet approved, in 4 countries (France, Italy, UK and US).

Design/Methods:

LNGT was provided based on patient/physician requests and its use was authorized by local/national regulations. Patients received LNGT as a unilateral or bilateral intravitreal injection. Baseline characteristics, efficacy and safety data were collected.

Results:

A total of 63 ND4-LHON patients received LNGT in EAP, mainly in France (35 [55.6%]) and the US (18 [28.6%]). Most (42 [66.7%]) patients received bilateral injections. At the time of the first injection, patients were on average (SD) 33.7 (+/-16.6) years old, with 6 (9.5%) children aged 13 or 14 years. The mean (SD) duration of disease at the first injection was 11.4 (+/-9.6) months. Most (84.1%) patients were treated with idebenone at or after LNGT injection. Best-corrected visual acuity (BCVA) values at 1 year were obtained from 53 patients; the mean (SD) change in BCVA from nadir to 1 year was -0.42 (+/-0.54) LogMAR (+21 ETDRS letters). Clinically relevant recovery (CRR) from nadir was observed in 42.9% (30/70) of treated eyes within 12 months of disease onset, and in 76.5% (26/34) of treated eyes after 12 months of disease onset. The safety of LNGT was comparable to those of the 189 patients from clinical trial studies, with no difference in the incidence of intraocular inflammation between patients treated bilaterally and unilaterally (51.2% vs 52.4%).

Conclusions:

Injection of LNGT in the real-life setting was associated with a clinically meaningful improvement in visual acuity from nadir and a favorable safety profile.