Document Type
Article
Publication 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.
Recommended Citation
Biousse, Valérie; Newman, Nancy J; Yu-Wai-Man, Patrick; Carelli, Valerio; Moster, Mark; Vignal-Clermont, Catherine; Klopstock, Thomas; Sadun, Alfredo A; Sergott, Robert C; Hage, Rabih; Esposti, Simona; La Morgia, Chiara; Priglinger, Claudia; Karanja, Rustum; Blouin, Laure; Taiel, Magali; and Sahel, José-Alain, "Long-Term Follow-Up After Unilateral Intravitreal Gene Therapy for Leber Hereditary Optic Neuropathy: The RESTORE Study" (2021). Wills Eye Hospital Papers. Paper 138.
https://jdc.jefferson.edu/willsfp/138
Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.
PubMed ID
34415265
Language
English
Comments
This article is the author’s final published version in Journal of neuro-ophthalmology : the official journal of the North American Neuro-Ophthalmology Society, Volume 41, Issue 3, September 2021, Pages 309 - 315.
The published version is available at https://doi.org/10.1097/WNO.0000000000001367. Copyright © Biousse et al.