Abstract Details

Title Treatment Options for Acute/Subacute Patients with m.11778G>A MT-ND4 Leber Hereditary Optic Neuropathy: A Meta-analysis

Topic Neuro-ophthalmology/Neuro-otology

Presentation(s) P10 - Poster Session 10 (11:45 AM-12:45 PM)

Poster/Presentation
Number 10-006

Objective To assess the visual outcomes of patients with Leber hereditary optic neuropathy (LHON) harboring the m.11778G>A MT-ND4 mutation with no treatment (natural history), idebenone therapy, and lenadogene nolparvovec intravitreal injection.

Background Current treatment options for LHON are limited to idebenone, a therapy not approved in all countries. Lenadogene nolparvovec is a novel gene therapy for MT-ND4 LHON patients, not yet approved except for compassionate use.

Design/Methods Based on a pre-defined statistical analysis plan, three independent meta-analyses were performed on three groups of patients, with efficacy outcome being the clinically relevant recovery (CRR; on-chart best-corrected visual acuity [BCVA] gain of at least 10 ETDRS letters, or conversion from off-chart to on-chart BCVA) from nadir. For the natural history and idebenone groups, a systematic review of all available individual and aggregate data was performed, resulting in the inclusion of untreated patients from 5 studies and idebenone-treated patients from 6 studies. For the lenadogene nolparvovec group, patients were included from all phase 3 studies: RESCUE, REVERSE, RESTORE and REFLECT. An inverse-variance-weighted method was used to estimate an overall effect and its 95% confidence interval (CI) using random effects model.

Results For each meta-analysis, patients were mostly (≥80%) men, aged around 30 years at the time of vision loss. The CRR from nadir [95% CI] at eye level was estimated at 19% [9%; 32%] (n=173), 30% [20%; 41%] (n=201) and 58% [52%; 63%] (n=174) in untreated, idebenone-treated and lenadogene nolparvovec-treated patients, respectively. This gradient of recovery was also observed with CRR at the patient level (response in one or both eyes). There was no overlap in CRR 95% CIs when comparing lenadogene nolparvovec versus natural history and idebenone.

Conclusions There was a gradient of efficacy of visual recovery with lenadogene nolparvovec intravitreal gene therapy superior to idebenone treatment, and both superior to the natural history of the disease.

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.
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.
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.
Valerie Biousse, MD	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 $5,000-$9,999 for serving as a Consultant for Topcon. 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.
Catherine Vignal-Clermont (Hopital Fondation A de Rothschild)	Catherine Vignal-Clermont has nothing to disclose.
Francois Montestruc (eXYSTAT)	Francois Montestruc has received personal compensation for serving as an employee of eXYSTAT.
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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