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StudyThe British journal of ophthalmology · 2026

Efficacy of lenadogene nolparvovec gene therapy versus idebenone in Leber hereditary optic neuropathy due to the m.11778G>A MT-ND4 variant: two matching adjusted indirect comparisons.

Patrick Yu-Wai-Man, Nancy J Newman, Valerio Carelli … José-Alain Sahel

OphthalmologyStudy

Gene therapy linked to higher clinically relevant visual recovery at 24 months than idebenone

Efficacy of lenadogene nolparvovec gene therapy versus idebenone in Leber hereditary optic neuropathy due to the m.11778G>A MT-ND4 variant: two matching adjusted indirect comparisons.

Patrick Yu-Wai-Man … José-Alain Sahel

The British journal of ophthalmology · 2026

Background

Lenadogene nolparvovec is an intravitreal gene therapy for patients with Leber hereditary optic neuropathy (leber hereditary optic neuropathy) carrying the m.11778G>A MT-ND4 variant.

Purpose

To estimate the relative effects of both treatments, we performed two matching adjusted indirect comparisons (matching adjusted indirect comparisons) between idebenone aggregated data from the LEROS study and expanded access programme (expanded access programme), and lenadogene nolparvovec individual data from the REFLECT study (bilateral treatment).

Methods

Matching covariates included age at disease onset, sex, baseline best-corrected visual acuity (BCVA), and time from vision loss to treatment.

Results

gene therapy patients recovered meaningful vision far more often than idebenone patients

OR by subgroup · 95% CI

More results

No statistically significant difference was observed for time to initial clinically relevant recovery and change from baseline BCVA at 24 months.

For the matching adjusted indirect comparisons expanded access programme versus REFLECT, there was a low overlap between the two populations related to a difference in the time from vision loss to treatment.

More results

In a post hoc sensitivity analysis comparing expanded access programme to RESCUE data (effective sample size: 33), clinically relevant recovery was 39.0% for idebenone versus 69.5% for lenadogene nolparvovec (OR=3.59, 95% CI 1.42 to 9.06; p=0.011).

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Conclusion

The two matching adjusted indirect comparisons demonstrated a clinically meaningful higher visual recovery at 24 months with lenadogene nolparvovec than with idebenone in patients with leber hereditary optic neuropathy due to the m.11778G>A MT-ND4 variant.

Post

Efficacy of lenadogene nolparvovec gene therapy versus idebenone in Leber hereditary optic neuropathy due to the m.11778G>A MT-ND4 variant: two matching adjusted indirect comparisons.

Gene therapy linked to higher clinically relevant visual recovery at 24 months than idebenone

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