Abstract Details

Title Lenadogene Nolparvovec Gene Therapy for Leber Hereditary Optic Neuropathy in the Real-life Setting

Topic Neuro-ophthalmology/Neuro-otology

Presentation(s) S18 - Neuro-ophthalmology/Neuro-otology (3:54 PM-4:06 PM)

Poster/Presentation
Number 003

Objective To provide efficacy and safety data on the use of lenadogene nolparvovec gene therapy (LNGT) in real-life conditions in patients with Leber hereditary optic neuropathy (LHON) caused by the m.11778G>A ND4 variant.

Background Early access programs (EAP) allowed patients with ND4-LHON to benefit from LNGT, which is not yet approved, in 4 countries (France, Italy, UK and US).

Design/Methods LNGT was provided based on patient/physician requests and its use was authorized by local/national regulations. Patients received LNGT as a unilateral or bilateral intravitreal injection. Baseline characteristics, efficacy and safety data were collected.

Results A total of 63 ND4-LHON patients received LNGT in EAP, mainly in France (35 [55.6%]) and the US (18 [28.6%]). Most (42 [66.7%]) patients received bilateral injections. At the time of the first injection, patients were on average (SD) 33.7 (+/-16.6) years old, with 6 (9.5%) children aged 13 or 14 years. The mean (SD) duration of disease at the first injection was 11.4 (+/-9.6) months. Most (84.1%) patients were treated with idebenone at or after LNGT injection. Best-corrected visual acuity (BCVA) values at 1 year were obtained from 53 patients; the mean (SD) change in BCVA from nadir to 1 year was -0.42 (+/-0.54) LogMAR (+21 ETDRS letters). Clinically relevant recovery (CRR) from nadir was observed in 42.9% (30/70) of treated eyes within 12 months of disease onset, and in 76.5% (26/34) of treated eyes after 12 months of disease onset. The safety of LNGT was comparable to those of the 189 patients from clinical trial studies, with no difference in the incidence of intraocular inflammation between patients treated bilaterally and unilaterally (51.2% vs 52.4%).

Conclusions Injection of LNGT in the real-life setting was associated with a clinically meaningful improvement in visual acuity from nadir and a favorable safety profile.

Authors/Disclosures
Nancy J. Newman, MD, FAAN (Emory University School of Medicine) PRESENTER	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 $5,000-$9,999 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 Stoke. Dr. Newman has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Eli Lilly. Dr. Newman has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Phelcom. The institution of Dr. Newman has received research support from GenSight. 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.
Catherine Vignal-Clermont (Hopital Fondation A de Rothschild)	Catherine Vignal-Clermont has nothing to disclose.
Chiara La Morgia, MD (University of Bologna)	Dr. La Morgia has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Regulatory Pharmanet s.r.l. . Dr. La Morgia has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Santhera Pharmaceuticals. Dr. La Morgia has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Chiesi Farmaceutici s.p.a.. The institution of Dr. La Morgia has received research support from Italian Ministry of Health.
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.
Patrick Yu-Wai-Man	Patrick Yu-Wai-Man has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for GenSight Biologics. Patrick Yu-Wai-Man has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Chiesi. Patrick Yu-Wai-Man has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Stoke Therapeutics. Patrick Yu-Wai-Man has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for PYC Therapeutics.
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.
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.
Sarah Thornton, MD	Dr. Thornton has received personal compensation for serving as an employee of Tuberous Sclerosis Alliance .
Magali Taiel	Magali Taiel has received personal compensation for serving as an employee of GenSight Biologics.
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 LightStone Ventures. 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 Avista. Jose-Alain Sahel has stock in Tenpoint. Jose-Alain Sahel has stock in SharpEye. Jose-Alain Sahel has stock in GenSight. Jose-Alain Sahel has received intellectual property interests from a discovery or technology relating to health care.

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