GenSight Biologics Reports Positive Data from Late-Stage Gene Therapy Trial in Rare Eye Disease

Rare Daily Staff

GenSight Biologics reported positive results from its late-stage clinical trial, which evaluates the safety and efficacy of a single intravitreal injection of GS010 its gene therapy for Leber Hereditary Optic Neuropathy (LHON).

LHON is caused by defects in mitochondrial genes encoding for proteins called NADH dehydrogenase. About 95 percent of LHON cases are due to mutations in the mitochondrial genes ND1, ND4 and ND6, which encode proteins of the respiratory chain Complex I, an important component of energy production within the mitochondrion and therefore the cell. The ND4 mutation is responsible for the majority of LHON cases, representing around 70 percent in Europe and North America and 80 to 85 percent in Asia. Onset of vision loss due to LHON typically occurs between 15 and 35 years of age. Vision loss often occurs in a sequential fashion where one eye is affected first, followed by the second eye on average two months later.

GS010 is an AAV2 gene therapy vector that encodes the human wild-type ND4 protein, which we are developing as a treatment of LHON caused by mutation of the ND4 gene.

The company said the results at 72 weeks from its REVERSE phase 3 trial show a clinically meaningful improvement from baseline in mean visual acuity in 37 subjects whose visual loss due to 11778-ND4 Leber Hereditary Optic Neuropathy.

The study used the Logarithm of the Minimal Angle of Resolution scores, a measure based on the number of letters patients read on the ETDRS chart. At 72 weeks, patients treated with the gene therapy had a mean visual acuity of +15 letters. That compared to a +12-letter improvement in eyes treated with a placebo.

“We’re seeing visual function continue to improve one and a half years after eyes are treated with GS010, and at the same time, objective tests continue to establish neuroprotection of the retina in treated eyes,” said Bernard Gilly, co-founder and CEO of GenSight. “This is, beyond any doubt, a great benefit for patients and their families. These results strengthen our determination to work with regulatory agencies to bring GS010 to market within our defined timelines.”

As per protocol, all 37 subjects will be evaluated again at 96 weeks, and data will be reported in the second quarter of 2019.

October 19, 2018
Photo: Bernard Gilly, co-founder and CEO of GenSight