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 meta-analyses comparing visual outcomes among patients with Leber Hereditary Optic Neuropathy (LHON) caused by a mutation in the MT-ND4 mitochondrial gene (ND4-LHON), the most common mutation leading to the poorest visual prognosis1.
The paper, published in the peer-reviewed journal Survey of Ophthalmology, is the first to compare the efficacy of LHON treatments, approved or in development, on visual outcomes in the ND4-LHON patient population and to compare these outcomes with those in untreated (natural history) patients. The meta-analyses establish a “gradient of efficacy” in two measures of visual outcomes assessed in the paper, with LUMEVOQ® gene therapy having better outcomes compared to idebenone treatment and both treatments having better outcomes compared to the natural history of the disease.
As measured by the rate of Clinically Relevant Recovery (CRR)2, which is the responder rate common across the studies analyzed in the paper, the rate of visual recovery after LUMEVOQ® gene therapy is triple that in the natural evolution of ND4-LHON and substantially greater than that among idebenone-treated patients.
Figure 1. “A Gradient of Efficacy”: Visual Recovery (CRR from Nadir) Among ND4-LHON Patients (Graphic: Business Wire)
“This study is very important for comparing these therapies’ abilities to achieve visual function outcomes in ND4-LHON patients,” commented Dr. Nancy J. Newman, LeoDelle Jolley Professor of Ophthalmology and Neurology at the Emory University School of Medicine in Atlanta, United-States, and lead author. “For the first time, we clearly demonstrate a gradient of efficacy in visual outcomes, more marked for Clinically Relevant Recovery (CRR) than for final Best-Corrected Visual Acuity (BCVA), with lenadogene nolparvovec gene therapy superior to idebenone treatment, and both superior to the natural history of the disease.”
The article updates an earlier set of findings, presented at the 2024 North American Neuro-Ophthalmology Society annual meeting, by including data from the recently published LEROS trial for idebenone and by including an assessment of final Best-Corrected Visual Acuity (BCVA) outcomes among the three groups of patients.
Figure 1. “A Gradient of Efficacy”: Visual Recovery (CRR2 from Nadir3) Among ND4-LHON Patients4,5
(See Figure 1)
The meta-analyses are the largest comprehensive review of the available data on the natural history of patients with vision loss from the MT-ND4 LHON mutation and those treated with idebenone, as well as all the available results on the efficacy of lenadogene nolparvovec gene therapy. The ND4-LHON population included in each group was representative of the typical demographics of the disease as reported in a century and a half of literature. In the natural evolution of the disease, most ND4-LHON patients experience a severe and chronic reduction in visual acuity in both eyes, which seriously affects their quality of life.
