GenSight Biologics’ retinal gene therapy could potentially treat optic neuropathy patients

In News by

GenSight Biologics has announced interim results of its REVERSE study, a Phase 3 clinical trial designed to evaluate GS010 in the treatment of Leber’s Hereditary Optic Neuropathy (LHON). Although the treatment was safe and tolerable, the study did not meet the primary end point. Favorable results of secondary endpoints have led the investigators to study the mechanism further.

LHON is a rare genetic disorder affecting the retinal ganglion cells leading to a persistent and severe bilateral loss of visual acuity within weeks or months. The disease is caused by point mutations in the mitochondrial DNA. GenSight’s GS010 uses a mitochondrial targeting sequence proprietary technology platform which, when associated with the gene of interest, allows the platform to specifically address defects inside the mitochondria using an adeno-associated vector.

GenSight Biologics is a Paris-based clinical-stage biotechnology company focusing on developing gene therapies for retinal diseases and diseases of the central nervous system.

REVERSE is a randomized, double-masked, sham-controlled, multi-center trial conducted in 37 patients with an onset of vision loss of 6-12 months. Latest results from the trial showed a favourable safety and tolerability profile for GS010. Although the treatment was safe, the study did not meet the primary end point, which was defined as the difference of improvement in visual acuity in GS010-treated eyes compared to sham-treated eyes at 48 weeks. Clinically meaningful improvement of +11 ETDRS letters was observed in both GS010-treated eyes and sham-treated eyes at 48 weeks compared to baseline in all subjects. The improvement of visual acuity in sham-treated eyes was unexpected and the company is further investigating the chance of a bilateral treatment effect in the untreated eye.

Secondary endpoints were measured using high resolution Spectral-Domain Optical Coherence Tomography (SD-OCT) and showed a statistically significant difference in retinal ganglion cell macular volume in GS010-treated eyes from baseline to week 48. Over the course of 48 weeks, sham-treated eyes lost a thickness of 3.4 μm of the retinal nerve fiber layer compared to baseline while GS010-treated eyes had a limited loss of 0.6 μm. Patients in the trial will be monitored for another 4 years.

Other than the REVERSE trial, GS010 is currently being investigated in two additional Phase 3 trials: RESCUE and REFLECT. RESCUE is designed to evaluate the safety and efficacy of a single intravitreal injection of GS010 in subjects affected by LHON with < 6 months of onset of vision loss. GenSight expects to report topline data for RESCUE in the third quarter of 2018. REFLECT is evaluating the safety and efficacy of bilateral injections of GS010 in patients with < 1 year of onset of vision loss in LHON. The first patient in REFLECT was treated last month.

Source: GenSight Biologics announces topline results from REVERSE Phase III clinical trial of GS010 in patients with Leber Hereditary Optic Neuropathy (LHON); Press Release