19 October 2018 - - French biopharma company GenSight Biologics (PAR: SIGHT) reported additional results at Week 72 from the REVERSE Phase III clinical trial, which evaluates the safety and efficacy of a single intravitreal injection of GS010 (rAAV2/2-ND4) in 37 subjects whose visual loss due to 11778-ND4 Leber Hereditary Optic Neuropathy commenced between 6 and 12 months prior to study treatment, the company said.

At 72 weeks, a clinically meaningful improvement from baseline in mean visual acuity of +15 letters (-0.294 LogMAR) was observed in GS010-treated eyes, with concomitant contralateral improvement of +12 letters (-0.246 LogMAR) in sham-treated eyes.

This improvement, which extends the positive trend that had been reported at Week 48, points to a sustained functional outcome for the trial subjects.

Continued improvement was also observed in contrast sensitivity as determined by Pelli-Robson low-contrast testing.

At 72 weeks, GS010-treated eyes and sham-treated eyes gained on average +0.21 LogCS and +0.15 LogCS versus baseline, respectively. The proportion of treated eyes that achieved a clinically meaningful improvement of at least 0.3 LogCS (45.9%) was statistically significantly higher than that of sham-treated eyes (24.3%; p=0.0047).

The visual function outcomes were accompanied by evidence that GS010 was engaging its anatomic targets, the ganglion cells. At 72 weeks, high-resolution Spectral-Domain Optical Coherence Tomography (SD-OCT) objectively demonstrated sustained preservation of the retina anatomy relevant to LHON in GS010-treated eyes.

The ganglion cell layer macular volume was preserved (+0.000 mm3) in treated eyes, while sham-treated eyes deteriorated from baseline (-0.044 mm3).

The difference was statistically significant (p=0.0060). Drug-treated eyes also showed a limited loss in thickness of the temporal quadrant of the retinal fiber layer of -1.6 µm, compared to a loss of -3.6 µm in sham-treated eyes (p=0.0521).

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

Topline 48-week data for RESCUE, the second Phase III clinical trial of GS010 in the treatment of LHON, is expected in early 1Q19.

GenSight Biologics S.A. is a clinical-stage biopharma company focused on discovering and developing innovative gene therapies for retinal neurodegenerative diseases and central nervous system disorders.
The company's pipeline leverages two core technology platforms, the Mitochondrial Targeting Sequence and optogenetics to help preserve or restore vision in patients suffering from blinding retinal diseases.

GenSight Biologics' lead product candidate, GS010, is in Phase III trials in Leber Hereditary Optic Neuropathy, a rare mitochondrial disease that leads to irreversible blindness in teens and young adults.

Using its gene therapy-based approach, GenSight Biologics' product candidates are designed to be administered in a single treatment to each eye by intravitreal injection to offer patients a sustainable functional visual recovery.

GS010 targets Leber Hereditary Optic Neuropathy by leveraging a mitochondrial targeting sequence proprietary technology platform, arising from research works conducted at the Institut de la Vision in Paris, which, when associated with the gene of interest, allows the platform to specifically address defects inside the mitochondria using an AAV vector (Adeno-Associated Virus).

The gene of interest is transferred into the cell to be expressed and produces the functional protein, which will then be shuttled to the mitochondria through specific nucleotidic sequences in order to restore the missing or deficient mitochondrial function.