Abstract Details

Two phase 3 clinical studies, RESCUE and REVERSE, assessed the efficacy and safety of an intravitreal injection of lenadogene nolparvovec. RESTORE is their long-term follow-up study.

To assess the long-term safety and efficacy of lenadogene nolparvovec gene therapy in patients with Leber hereditary optic neuropathy (LHON) due to the m.11778G>A ND4 mutation.

In RESCUE/REVERSE, all patients were treated with lenadogene nolparvovec in one eye and with sham injection in the other eye. After 96 weeks, patients were offered to participate in RESTORE for another 3 years, corresponding to 5 years post-treatment administration. Quality of life was monitored using the visual function questionnaire-25 (NEI VFQ-25).

Of the 72 patients who completed RESCUE or REVERSE, 62 participated in RESTORE. Patients were mostly male (79.0%) and had a mean (SD) age of 37.1 (15.3) years. Five years after treatment, the bilateral improvement from nadir observed 2 years after treatment was maintained: the absolute mean change (SD) from nadir in BCVA was -0.44 (0.46) LogMAR (+ 22.0 letters equivalent) for lenadogene nolparvovec-treated eyes and -0.39 (0.36) LogMAR (+19.5 letters equivalent) for sham-treated eyes. Most patients (80.7%) had their BCVA on chart (i.e., ≤1.6 LogMAR) at 5 years. A clinically relevant response from nadir was observed in 71.0% of patients. A clinically meaningful overall improvement of quality of life was reported, with a mean gain of 7 points from baseline for the VFQ-25 composite score. The safety profile was favorable, similar to that observed during the first 2 years.

Long-term follow-up of MT-ND4-LHON patients who were unilaterally treated with lenadogene nolparvovec demonstrated a sustained improvement of BCVA in both eyes and improvement of quality of life up to 5 years after treatment.