GenSight Biologics Reports Final REALITY Study Confirms Poor Spontaneous Recovery for LHON Patients with ND4 mutation

GenSight Biologics reported results from the final analysis of the REALITY natural history study, which reaffirm the poor prognosis for the vast majority of Leber Hereditary Optic Neuropathy (LHON) patients with vision loss due to a mutated ND4mitochondrial gene.

“The REALITY findings bolster the case that the improvements we saw in REVERSE, RESCUE and the first analysis of CLIN06 could not have arisen simply from spontaneous recovery among LHON patients,” Bernard Gilly, Co-founder and Chief Executive Officer of GenSight, said in a company news release. “We intend to bring this and other scientific evidence to the authorities to make a robust and convincing argument about the outstanding therapeutic benefit delivered by Lumevoq.”

Lumevoq (GS010), the gene therapy developed by GenSight Biologics for the treatment of vision loss in patients with LHON caused by a mutated ND4 mitochondrial gene, is on track to be submitted for European marketing authorization in September 2020.

Statistical analysis of the visual acuity in 23 REALITY subjects aged 15 or older with a mutated ND4 gene shows that on average, vision failed to recover from an initial sudden decline, even several years after vision loss. The sharp deterioration followed by an extended period of low visual acuity stands in sharp contrast with the improvements observed in the Lumevoq RESCUE and REVERSE trials.

“The REALITY results are entirely in keeping with a recent meta-analysis currently in press in the Journal of Neuro-Ophthalmology*, which showed that only about 11% of ND4 LHON patients have some degree of meaningful spontaneous improvement in vision,” noted Dr. Nancy Newman, LeoDelle Jolley Professor of Ophthalmology and Neurology at the Emory University School of Medicine in Atlanta, GA, USA, and one of the leading authorities on LHON.

REALITY was a retrospective and cross-sectional observational study of subjects with LHON, conducted in centers across Spain, Italy, France, United Kingdom, and the United States. The objective was to generate insights about the natural history of the disease based on an approach that would facilitate comparisons with REVERSE and RESCUE. The study aimed to enroll 50 subjects, but enrollment was curtailed due to measures taken to protect patients in the COVID-19 pandemic.

Of the 44 subjects who were enrolled before the COVID-19 measures took effect, 23 were 15 years old or older at the time of vision loss due to their mutated ND4 gene. Of these 23 ND4 subjects, 15 had been treated with idebenone, the majority within 12 months of their vision loss.

The RESCUE and REVERSE pivotal trials evaluated the efficacy and safety of a single intravitreal injection of Lumevoq in LHON subjects who were at 0-6 months and 6-12 months, respectively, from onset of vision loss due to carrying a mutated ND4 mitochondrial gene. 61 of the RESCUE and REVERSE subjects accepted the invitation for long-term follow-up in the CLIN06 trial, which recently reported initial results.

*N.J. Newman, V. Carelli, M. Taiel, P. Yu-Wai-Man. Visual outcomes in Leber hereditary optic neuropathy patients with the m. 11778>A (MTND4) mitochondrial DNA mutation. J Neuroophthalmol. In press (2020)