Long-Term Follow-Up After Unilateral Intravitreal Gene Therapy for Leber Hereditary Optic Neuropathy: The RESTORE Study.

Authors

• Valérie Biousse
• Nancy J Newman
• Patrick Yu-Wai-Man
• Valerio Carelli
• Mark L Moster
• Catherine Vignal-Clermont
• Thomas Klopstock
• Alfredo A Sadun
• Robert C Sergott
• Rabih Hage
• Simona Esposti
• Chiara La Morgia
• Claudia Priglinger
• Rustum Karanja
• Laure Blouin
• Magali Taiel
• José-Alain Sahel

Publication/Presentation Date

9-1-2021

Abstract

BACKGROUND: RESCUE and REVERSE were 2 Phase 3 clinical trials that assessed the efficacy and safety of intravitreal gene therapy with lenadogene nolparvovec (rAAV2/2-ND4) for the treatment of Leber hereditary optic neuropathy (LHON). RESTORE is the long-term follow-up study of subjects treated in the RESCUE and REVERSE trials.

METHODS: In RESCUE and REVERSE, 76 subjects with LHON because of the m.11778 G>A mutation in the mitochondrial gene ND4 received a single unilateral intravitreal injection of lenadogene nolparvovec. After 96 weeks, 61 subjects were enrolled in the long-term follow-up study RESTORE. The best-corrected visual acuity (BCVA) was assessed over a period of up to 52 months after onset of vision loss. A locally estimated scatterplot smoothing regression model was used to analyze changes in BCVA over time. Vision-related quality of life was reported using the visual function questionnaire-25 (VFQ-25).

RESULTS: The population of MT-ND4 subjects enrolled in RESTORE was representative of the combined cohorts of RESCUE and REVERSE for mean age (35.1 years) and gender distribution (79% males). There was a progressive and sustained improvement of BCVA up to 52 months after the onset of vision loss. The final mean BCVA was 1.26 logarithm of the minimal angle of resolution 48 months after the onset of vision loss. The mean VFQ-25 composite score increased by 7 points compared with baseline.

CONCLUSION: The treatment effect of lenadogene nolparvovec on BCVA and vision-related quality of life observed 96 weeks (2 years) after treatment in RESCUE and REVERSE was sustained at 3 years in RESTORE, with a maximum follow-up of 52 months (4.3 years) after the onset of vision loss.

Volume

41

Issue

3

First Page

309

Last Page

315

ISSN

1536-5166

Published In/Presented At

Biousse, V., Newman, N. J., Yu-Wai-Man, P., Carelli, V., Moster, M. L., Vignal-Clermont, C., Klopstock, T., Sadun, A. A., Sergott, R. C., Hage, R., Esposti, S., La Morgia, C., Priglinger, C., Karanja, R., Blouin, L., Taiel, M., Sahel, J. A., & LHON Study Group (2021). Long-Term Follow-Up After Unilateral Intravitreal Gene Therapy for Leber Hereditary Optic Neuropathy: The RESTORE Study. Journal of neuro-ophthalmology : the official journal of the North American Neuro-Ophthalmology Society, 41(3), 309–315. https://doi.org/10.1097/WNO.0000000000001367

Disciplines

Business Administration, Management, and Operations | Health and Medical Administration | Management Sciences and Quantitative Methods

PubMedID

34415265

Department(s)

Administration and Leadership

Document Type

Article