Gene Therapy Shows Durable Bilateral Improvements in Leber Hereditary Optical Neuropathy


The long-term RESTORE study included data from 55 participants in previous phase 3 trials.

The gene therapy lenadogene nolparvovec (GS010; LUMEVOQ; GenSight Biologics) has showed durable vision improvements in people with Leber Hereditary Optical Neuropathy (LHON) enrolled in the long-term follow-up (LTFU) RESTORE study.

“The 5-year data from the RESTORE long-term extension study illustrates that the efficacy and safety data previously reported following treatment with a one-time injection of LUMEVOQ® is being maintained, providing hope to patients affected with this debilitating blinding disease” Patrick Yu-Wai-Man, MD, PhD, Professor of Ophthalmology and Honorary Consultant Neuro-ophthalmologist, University of Cambridge, Moorfields Eye Hospital, and UCL Institute of Ophthalmology, United Kingdom, said in a statement.

RESTORE included 55 participants from the RESCUE (NCT02652767) and REVERSE (NCT02652780) phase 3 trials and provided 5-year efficacy, safety, and durable data. Participants had LHON caused by a mutated ND4 mitochondrial gene and received an intravitreal injection of S010 in 1 eye and and sham injection in the other. Participants were enrolled in RESTORE 2 years after treatment with GS010.

Prior to the LTFU, participants hada mean 18.8-letter improvement in Early Treatment Diabetic Retinopathy Study (ETDRS) scale from the mean nadir of best-corrected visual acuity (BCVA) in treated eyes and a mean 17.4-letter improvement in ETDRS in sham-treated eyes. After 5 years of follow-up, investigators found that the bilateral improvement in BCVA has been sustained, with a mean improvement against nadir of +22.0 letters in treated eyes and a mean improvement of +19.5 letters in sham-treated eyes.

WATCH NOW: Targeting LHON and Retinitis Pigmentosa With Gene Therapy

Visual improvements were supported by clinically meaningful increases in self-reported quality of life (QoL) scores at 5 years after treatment compared to baseline. Increases were driven by sub-scores corresponding to mental health and autonomy, including composite score, mental health, role difficulties, dependency, near and distance activities, general vision, and social functioning.

“The data so far showing the sustained efficacy of LUMEVOQ®, combined with a favorable safety profile, is fully consistent with clinical experts’ belief that the gene therapy’s effects will not wane after its administration” Magali Taiel, MD, chief medical officer, GenSight Biologics, added to the statement. “With even more confidence about the benefit we can deliver to patients, the GenSight team is working with full intensity to bring our therapy to patients as quickly and safely as possible.”

CGTLive previously spoke with Taiel about data from the phase 3 REFLECT trial (NCT03293524). Investigators found statistically significant improvements in visual acuity from baseline in the first affected eye with both unilateral (+0.15 LogMAR score [+8 ETDRS letters]; P <.05) and bilateral (+0.23 LogMAR score [+12 ETDRS letters]; = .001) injections.

GenSight Biologics reports 5 years’ data showing sustained efficacy and safety following one-time treatment with LUMEVOQ®. News release. GenSight Biologics. July 20, 2022.
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