Abstract Details

Title Efficacy of Lenadogene Nolparvovec Gene Therapy Versus Idebenone: A Matched Adjusted Indirect Comparison

Topic Neuro-ophthalmology/Neuro-otology

Presentation(s) S18 - Neuro-ophthalmology/Neuro-otology (4:06 PM-4:18 PM)

Poster/Presentation
Number 004

Objective To estimate the relative treatment effects of lenadogene nolparvovec gene therapy (LNGT) versus idebenone, we performed two matched adjusted indirect comparisons (MAICs) between idebenone aggregated data from the LEROS study and EAP program, and LNGT individual data from the REFLECT study (bilateral treatment).

Background Lenadogene nolparvovec is a not yet approved intravitreal gene therapy for patients with Leber hereditary optic neuropathy (LHON) carrying the m.11778G>A ND4 variant. Idebenone, a synthetic analog of coenzyme Q₁₀, is the only approved treatment for LHON.

Design/Methods Matching covariates included age at disease onset, sex, baseline best-corrected visual acuity (BCVA), and time from vision loss to treatment. The outcomes of interest were clinically relevant recovery (CRR) from nadir at 24 months, time to initial CRR, and change from baseline of BCVA at 24 months.

Results

For the MAIC LEROS vs REFLECT (effective sample size [ESS]: 77), a statistically higher CRR at 24 months was observed with LNGT compared with idebenone (60.4% vs 35.4%; OR=2.78, 95% CI [1.53; 5.06]; p=0.001). No statistically significant difference was observed between LNGT and idebenone for time to initial CRR and change from baseline BCVA at 24 months. For the MAIC EAP vs REFLECT, there was a low overlap between the two populations related to a difference in the time from vision loss to treatment (4.3 [2.7] vs 8.4 [3.4] months; p< 0.001). In a post-hoc sensitivity analysis comparing EAP to RESCUE (ESS: 33), CRR was 39.0% for idebenone vs 69.5% for LNGT (OR=3.59, [1.42; 9.06]; p=0.011).

Conclusions The two MAICs demonstrated a clinically meaningful higher visual recovery at 24 months with LNGT than with idebenone in ND4 patients.

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 $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.
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.
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 $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.
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.
Adeline Pierache	Mrs. Pierache 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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