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Abstract Details

Long-term Follow-up of m.11778G>A MT-ND4-LHON Patients Treated with Lenadogene Nolparvovec Ocular Gene Therapy: the RESTORE Study
Neuro-ophthalmology/Neuro-otology
S12 - Neuro-ophthalmology/Neuro-otology (11:51 AM-12:03 PM)
004

Two phase 3 clinical studies, RESCUE and REVERSE, assessed the efficacy and safety of an intravitreal injection of lenadogene nolparvovec. RESTORE is their long-term follow-up study.

To assess the long-term safety and efficacy of lenadogene nolparvovec gene therapy in patients with Leber hereditary optic neuropathy (LHON) due to the m.11778G>A ND4 mutation.

In RESCUE/REVERSE, all patients were treated with lenadogene nolparvovec in one eye and with sham injection in the other eye. After 96 weeks, patients were offered to participate in RESTORE for another 3 years, corresponding to 5 years post-treatment administration. Quality of life was monitored using the visual function questionnaire-25 (NEI VFQ-25).

Of the 72 patients who completed RESCUE or REVERSE, 62 participated in RESTORE. Patients were mostly male (79.0%) and had a mean (SD) age of 37.1 (15.3) years. Five years after treatment, the bilateral improvement from nadir observed 2 years after treatment was maintained: the absolute mean change (SD) from nadir in BCVA was -0.44 (0.46) LogMAR (+ 22.0 letters equivalent) for lenadogene nolparvovec-treated eyes and -0.39 (0.36) LogMAR (+19.5 letters equivalent) for sham-treated eyes. Most patients (80.7%) had their BCVA on chart (i.e., ≤1.6 LogMAR) at 5 years. A clinically relevant response from nadir was observed in 71.0% of patients. A clinically meaningful overall improvement of quality of life was reported, with a mean gain of 7 points from baseline for the VFQ-25 composite score. The safety profile was favorable, similar to that observed during the first 2 years.

Long-term follow-up of MT-ND4-LHON patients who were unilaterally treated with lenadogene nolparvovec demonstrated a sustained improvement of BCVA in both eyes and improvement of quality of life up to 5 years after treatment.

Authors/Disclosures
Valerie Biousse, MD
PRESENTER
Dr. Biousse has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Gensights Biologic. Dr. Biousse has received personal compensation in the range of $0-$499 for serving as a Consultant for Neurophoenix. The institution of Dr. Biousse has received research support from NIH. Dr. Biousse has received publishing royalties from a publication relating to health care. Dr. Biousse has received publishing royalties from a publication relating to health care.
Nancy J. Newman, MD, FAAN (Emory University School of Medicine) Dr. Newman has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for GenSight. Dr. Newman has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Chiesi. Dr. Newman has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Neurophoenix. Dr. Newman has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Stoke. Dr. Newman has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Avidity. Dr. Newman has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Neurophth. The institution of Dr. Newman has received research support from GenSight. The institution of Dr. Newman has received research support from Chiesi/Santhera. The institution of Dr. Newman has received research support from NINDS/NIH. Dr. Newman has received publishing royalties from a publication relating to health care. Dr. Newman has received publishing royalties from a publication relating to health care. Dr. Newman has received publishing royalties from a publication relating to health care.
Patrick Yu-Wai-Man Patrick Yu-Wai-Man has received personal compensation in the range of $500-$4,999 for serving as a Consultant for GenSight Biologics.
Valerio Carelli, MD, PhD (University of Bologna) Dr. Carelli has received personal compensation in the range of $0-$499 for serving as a Consultant for Chiesi Farmaceutici. Dr. Carelli has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Chiesi Farmaceutici.
Mark L. Moster, MD, FAAN (Neuro-Ophthalmology -Wills Eye Hospital) Dr. Moster has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Gensight . Dr. Moster has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Viridian. Dr. Moster has received personal compensation in the range of $10,000-$49,999 for serving as an Expert Witness for Kilcoyne and Nesbitt.
Catherine Vignal-Clermont, MD (Foundation Ophtalmologique A De Rothschild) Dr. Vignal-Clermont has nothing to disclose.
Thomas H. Klopstock, MD (University of Munich, Dept. of Neurology) Dr. Klopstock has received personal compensation in the range of $500-$4,999 for serving as a Consultant for GenSight Biologics. Dr. Klopstock has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Chiesi GmbH. Dr. Klopstock has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Chiesi GmbH. Dr. Klopstock has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Chiesi GmbH. Dr. Klopstock has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for GenSight Biologics.
Alfredo Sadun, MD (Doheny Eye Institute USC Sch.) Dr. Sadun has received publishing royalties from a publication relating to health care.
Robert C. Sergott, MD (Wills Eye Hospital) Dr. Sergott has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Roche. Dr. Sergott has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Horizon Therapeutics. Dr. Sergott has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Biogen.
Magali Taiel Magali Taiel has nothing to disclose.
Jose-Alain Sahel The institution of Jose-Alain Sahel has received personal compensation in the range of $50,000-$99,999 for serving as a Consultant for Avista. The institution of Jose-Alain Sahel has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Tenpoint . The institution of Jose-Alain Sahel has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for THE BOARD OF GENSIGHT. The institution of Jose-Alain Sahel has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for THE BOARD OF SPARINGVISION. Jose-Alain Sahel has stock in Prophesee. Jose-Alain Sahel has stock in Tilak Healthcare. Jose-Alain Sahel has stock in Sparing Vision. Jose-Alain Sahel has stock in Chronolife. Jose-Alain Sahel has stock in VegaVect Inc.. Jose-Alain Sahel has stock in Avista. Jose-Alain Sahel has stock in Tenpoint. Jose-Alain Sahel has stock in SharpEye. Jose-Alain Sahel has stock in GenSight. The institution of Jose-Alain Sahel has received research support from LabEx LIFESENSES (ANR-10-LABX-65). The institution of Jose-Alain Sahel has received research support from IHU FOReSIGHT (ANR-18-IAHU-01). The institution of Jose-Alain Sahel has received research support from ERC Synergy "HELMHOLTZ". Jose-Alain Sahel has received intellectual property interests from a discovery or technology relating to health care.