Use of lenadogene nolparvovec gene therapy for Leber hereditary optic neuropathy in early access programs

Abstract

Purpose : Lenadogene nolparvovec is a novel, as yet unapproved, gene therapy for patients with Leber hereditary optic neuropathy (LHON) due to the m.11778G>A MT-ND4 mutation. Through early access programs, patients with MT-ND4-LHON can benefit from lenadogene nolparvovec prior to marketing authorization.

Methods : Lenadogene nolparvovec was provided based on unsolicited requests and authorized for use by local regulations. Patients with confirmed MT-ND4-LHON received lenadogene nolparvovec as a unilateral or bilateral intravitreal injection at the dose of 9x10¹⁰ viral genomes/eye. Baseline characteristics, efficacy, and safety data were collected.

Results : Between August 2018 and March 2022, 63 MT-ND4-LHON patients received lenadogene nolparvovec in early access programs; 35 (55.6%) in France, 9 (14.3%) in Italy, 1 (1.6%) in the UK and 18 (28.6%) in the US. Overall, 42 (66.7%) patients were administered bilaterally; all but one received both injections on the same day. At first lenadogene nolparvovec injection, the mean (SD) age was 34.5 (16.6) years (median=31.2; range=13.5-74.7) and the loss of vision in the first affected eye had lasted for a mean of 11.4 (9.7) months (n=62). Idebenone therapy was ongoing in 72.6% of patients at the time of injection. Among the 63 patients, 47 reached the 1-year post treatment time point but BCVA values of 38 patients are available at 1 year. For these 38 MT-ND4-LHON patients, the mean (SD) change in BCVA from baseline to 1 year was -0.29 (0.67) LogMAR (+14.5 EDTRS letters equivalent), and 25 were bilaterally treated and improved their BCVA at 1 year by -0.36 (0.73) LogMAR (+18 ETDRS letters equivalent). The safety of lenadogene nolparvovec was favorable with data comparable to those of the 189 patients treated in clinical studies.

Conclusions : Patients receiving lenadogene nolparvovec in the early access programs were predominantly European and received therapy mostly in both eyes. Preliminary efficacy and safety analyses show that lenadogene nolparvovec injection was associated with a clinically meaningful improvement of visual acuity and a favorable safety similar to that observed in clinical studies.

This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.