GenSight Biologics Announces Publication on Predictors of Final Visual Outcome in Patients Treated with LUMEVOQ® Gene Therapy

Paris, France, Thursday, January 17, 2025, 3:00 pm CET – GenSight Biologics (Euronext: SIGHT, ISIN: FR0013183985, PEA-PME eligible), a biopharma company focused on developing and commercializing innovative gene therapies for retinal neurodegenerative diseases and central nervous system disorders, today announced the publication of an exploratory analysis aimed at identifying predictive factors of the final best-corrected visual acuity (BCVA) in patients with Leber hereditary optic neuropathy (LHON) caused by a mutated mt-ND4 gene, all of whom were treated with LUMEVOQ^®, the Company’s gene therapy investigational product for the treatment of ND4-LHON.

The paper, published in the July 2025 issue of the journal Investigational Ophthalmology and Visual Science, a journal of ARVO (the Association for Research in Vision and Ophthalmology), concluded that “better baseline BCVA value and baseline thicker GCL (macular ganglion cell layer) and RNFL (retinal nerve fiber layer) are key predictors of the improved BCVA 1.5 years after treatment” among patients treated with LUMEVOQ^® at least 6 months after disease onset. The authors performed univariate analyses on 113 eyes of patients in three Phase III studies (RESCUE, REVERSE and REFLECT), with BCVA at 1.5 years post-treatment as the dependent variable and age, gender, timing of treatment, baseline BCVA value and baseline optical coherence tomography (OCT) parameters as covariates.

“The study is the first to use spectral domain-optical coherence tomography (SD-OCT) and other clinical outcomes to identify predictive factors of BCVA changes 1.5 years after treatment,” noted Dr. Robert C. Sergott, MD, lead author; Departments of Ophthalmology and Neurology, Wills Eye Hospital and Thomas Jefferson University; and head of the Central Reading Center,  William H. Annesley, Jr., EyeBrain Center.[1] “The structural and functional evidence concurs that direct injection of lenadogene nolparvovec may be more effective than the contralateral therapeutic effect, thus supporting a recommendation to treat LHON patients bilaterally when possible.”

The analyses of OCT parameters also corroborated the finding that outcomes are better for patients who receive LUMEVOQ^® after 6 months from disease onset. That is, patients treated during the dynamic phase of the disease achieve better visual outcomes than patients treated during the subacute phase of the disease. The authors hypothesize that RNFL pseudoedema (swelling) during the subacute phase may hamper the diffusion of the viral vector to RGCs. In the dynamic phase of the disease, the stabilized retinal layers are  sufficiently preserved to optimize the transfection efficiency of RGCs and thus the effects of gene therapy.

The full article is available online on this link.

[1]The William H. Annesley, Jr., EyeBrain Center conducted OCT analyses for the RESCUE, REVERSE, RESTORE and REFLECT studies.