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

BACKGROUND: analogue, is the only approved treatment for LHON. To estimate the relative effects of both treatments, we performed two matching adjusted indirect comparisons (MAICs) between idebenone aggregated data from the LEROS study and expanded access programme (EAP), 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. The outcomes of interest were clinically relevant recovery (CRR) from nadir at 24 months, time to initial CRR and change from baseline BCVA at 24 months. RESULTS: For the MAIC LEROS versus REFLECT (effective sample size (ESS): 77), a statistically higher CRR at 24 months was observed with lenadogene nolparvovec compared with idebenone (60.4% vs 35.4%; OR=2.78, 95% CI 1.53 to 5.06; p=0.001). No statistically significant difference was observed for time to initial CRR and change from baseline BCVA at 24 months. For the MAIC EAP versus REFLECT, there was a low overlap between the two populations related to a difference in the time from vision loss to treatment. In a post hoc sensitivity analysis comparing EAP to RESCUE data (ESS: 33), CRR was 39.0% for idebenone versus 69.5% for lenadogene nolparvovec (OR=3.59, 95% CI 1.42 to 9.06; p=0.011). CONCLUSION: variant.

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Journal
British Journal of Ophthalmology
Published
2026-04-22
DOI
https://doi.org/10.1136/bjo-2025-329206
Primary Topic
Retinal Development and Disorders
Type
article
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article

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, François Montestruc, Magali Taiel, Adeline Piérache et al.
British Journal of Ophthalmology
Retinal Development and Disorders
article

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, François Montestruc, Magali Taiel, Adeline Piérache, José-Alain Sahel, Valerio Carelli, Valerie Biousse, Nancy J Newman
article en

Abstract

BACKGROUND: analogue, is the only approved treatment for LHON. To estimate the relative effects of both treatments, we performed two matching adjusted indirect comparisons (MAICs) between idebenone aggregated data from the LEROS study and expanded access programme (EAP), 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. The outcomes of interest were clinically relevant recovery (CRR) from nadir at 24 months, time to initial CRR and change from baseline BCVA at 24 months. RESULTS: For the MAIC LEROS versus REFLECT (effective sample size (ESS): 77), a statistically higher CRR at 24 months was observed with lenadogene nolparvovec compared with idebenone (60.4% vs 35.4%; OR=2.78, 95% CI 1.53 to 5.06; p=0.001). No statistically significant difference was observed for time to initial CRR and change from baseline BCVA at 24 months. For the MAIC EAP versus REFLECT, there was a low overlap between the two populations related to a difference in the time from vision loss to treatment. In a post hoc sensitivity analysis comparing EAP to RESCUE data (ESS: 33), CRR was 39.0% for idebenone versus 69.5% for lenadogene nolparvovec (OR=3.59, 95% CI 1.42 to 9.06; p=0.011). CONCLUSION: variant.

British Journal of Ophthalmology
Centre National de la Recherche Scientifique (FR), Moorfields Eye Hospital NHS Foundation Trust (GB), Institut de la Vision (FR), Emory University (US), Inserm (FR), University of Pittsburgh (US), University of Cambridge (GB), Centre hospitalier national d'ophtalmologie des Quinze-Vingts (FR), Cambridge University Hospitals NHS Foundation Trust (GB), Sorbonne Université (FR), Fondation Ophtalmologique Adolphe de Rothschild (FR), GenSight Biologics (France) (FR), Istituto delle Scienze Neurologiche di Bologna (IT), Moorfields Eye Hospital (GB), Addenbrooke's Hospital (GB), Neurological Surgery (US), University College London (GB), MRC Mitochondrial Biology Unit (GB), University of Bologna (IT)
Research to Prevent Blindness, Emory University, LifeArc, Horizon Therapeutics, National Institute for Health and Care Research, Sight Research UK, Fight for Sight UK, Rosetrees Trust, Ministero della Salute, Isaac Newton Trust, Moorfields Eye Hospital NHS Foundation Trust, Moorfields Eye Charity, National Institutes of Health, School of Medicine, Emory University, Addenbrooke's Charitable Trust, Cambridge University Hospitals, NIHR Cambridge Biomedical Research Centre, GENSIGHT BIOLOGICS PARIS
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