Phase 1/2 Study of Gene Therapy to Treat LHON Showing Promise in Those with Early Disease Onset

Margarida Azevedo, MSc avatar

by Margarida Azevedo, MSc |

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LHON disease

GenSight Biologics released new preliminary findings from a Phase 1/2 clinical trial assessing the safety and tolerability of the company’s lead investigational gene therapy, GS010, in patients with Leber’s hereditary optic neuropathy (LHON), a maternally inherited mitochondrial disease causing irreversible vision loss. The data show significant improvement for those in earlier stages of the disease.

GS010 is an AAV2 (adeno-associated virus) containing the human wild-type ND4 gene, being developed to treat LHON associated with mutations in this gene.

GS010 enables an efficient expression of the ND4 gene by encoding for a protein that is normally produced in the mitochondria. Specifically, ND4 is flanked by a mitochondrial targeting sequence (MTS) platform (developed at the Institut de la Vision, in France),  which allows the specific correction of defects. This results in the synthesis of a functional ND4 protein.

“These preliminary data at 48 weeks give significant hope to patients suffering from LHON, a very severe disease with no existing curative treatment,” Dr. Catherine Vignal, a study investigator and head of the Department of Ophthalmology at the Rothschild Foundation Hospital in Paris, said in a press release.

Fifteen treated patients in the ongoing Phase 1/2 trial (NCT02064569) were divided into groups of three. Each group was treated with an increasing dose of GS010 through a single injection in the eye most affected by the disease. Visual acuity was assessed by reading letters on a chart.

At 48 weeks after treatment, LHON patients who had the disease for less than two years showed a gain of +30 letters  in the treated eye, and a gain of +13 letters in the untreated eye. No significant change in visual acuity, however, was reported in those with disease onset of more than two years (on average, trial participants had the disease for six years).

Combined effects of GS010 stabilizes at 48 weeks post-injection, the company reported. The trial is expected to conclude in February 2019.

“This preliminary data is very encouraging and validates the design of the two Phase III studies currently ongoing in the US and Europe on GS010 for the treatment of Leber’s Hereditary Optic Neuropathy” said Bernard Gilly, CEO and co-founder of GenSight. “Moreover, these results support the potential of our mitochondrial targeting sequence technology platform or MTS, and allows us to envision other applications in diseases involving defects of the mitochondrion, in ophthalmology as well as in other therapeutic areas.”

Those Phase 3 studies (called RESCUE in Europe, Reverse in the U.S.), now recruiting patients, will evaluate the efficacy of GS010 in LHON patients with an ND4 mutation and disease onset of less than one year. Top-line data are expected to be released in late 2017.

LHON, a mitochondria inherited disease, is characterized by degeneration of retinal ganglion cells and their axons, leading to an acute or subacute loss of central vision. The condition often starts in early adulthood, and predominantly affects males.