PARIS– 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 that the Journal of Neuro-Ophthalmology has published a paper on a cross-sectional analysis of the baseline (pre-treatment) characteristics of the ND4-LHON subjects enrolled in the RESCUE and REVERSE Phase III trials of LUMEVOQ®.
The paper*, published in the September issue under the title “Cross‑Sectional Analysis of Baseline Visual Parameters in Subjects Recruited into the RESCUE and REVERSE ND4-LHON Gene Therapy Studies”, confirms drastic loss of visual function and anatomy in the year after onset of vision loss due to Leber hereditary optic neuropathy (LHON) caused by the G11778A mutation in the ND4 gene.
“This cross-sectional analysis of patients with strict examination protocols demonstrates that once symptomatic with ND4-LHON, visual acuity and retinal structures rapidly deteriorate over months to a level of legal blindness,” commented lead author Dr. Mark L. Moster, MD, Department of Neuro-Ophthalmology, Wills Eye Hospital and Professor of Neurology and Ophthalmology at Thomas Jefferson University, Philadelphia, United-States. Dr. Moster, who was also an Investigator in the RESCUE and REVERSE trials, added, “These findings emphasize the need for early diagnosis and potential gene therapy in these patients.”
GenSight Biologics’ gene therapy LUMEVOQ® was submitted for marketing approval in Europe in September 2020 after RESCUE and REVERSE demonstrated visual acuity improvements among patients treated with LUMEVOQ®.
The cross-sectional analysis of baseline data showed that best-corrected visual acuity (BCVA) values substantially worsened in the first 8 months after onset of vision loss and were globally off-chart after 8 months of vision loss. Linear regression analysis of individual data points showed that each month of vision loss was associated with a mean visual acuity loss of +0.24 LogMAR (-12 ETDRS letters equivalent) in the eyes of untreated RESCUE patients with less than 6 months of vision loss. In the eyes of untreated REVERSE patients with 6 to 12 months of vision loss, each month was associated with little further visual acuity deterioration (on average +0.02 LogMAR, -1 ETDRS letter equivalent).
When the RESCUE and REVERSE sub-samples were compared, mean visual acuity, contrast sensitivity, and parameters of retinal anatomy measured by spectral-domain optical coherence tomography (SD-OCT) were significantly worse in eyes with 6 to 12 months of vision loss, compared to those in eyes with up to 6 months of vision loss.
The baseline data were collected on two pre-injection visits among the 76 subjects in the RESCUE and REVERSE clinical trials. At enrollment, subjects were over 15 years old and had between 0 and 6 months of vision loss in RESCUE, and 6 to 12 months of vision loss in REVERSE. Baseline data were grouped and averaged according to time since onset of vision loss, in order to describe the variation of visual parameters over the first year after disease onset.
The findings reinforce the medical consensus on the natural history of LHON over the first year post-vision loss, in which an acute phase of visual decline in the first months after onset is followed by a relative stabilization of visual acuity in the dynamic phase of the disease.a This pattern, in combination with the very low rate of spontaneous partial recovery of visual acuity in patients with the G1178A mutation and later onset (at 15 and over)b, suggests that ND4-LHON patients matching the RESCUE and REVERSE populations have an acute need for therapeutic intervention.
