RARE Daily

GenSight Will Seek Approval for Gene Therapy for Rare Eye Disease Strength of Sham Treatment

May 29, 2019

GenSight said it was preparing for a pre-submission meeting with the European Medicines Agency and an end-of-phase 2 meeting with the U.S. Food and Drug Administration to advance GS010, its gene therapy for the inherited eye disease Leber hereditary optic neuropathy.

The effort to advance the therapy comes despite the strength a sham treatment showed in its clinical study failing to demonstrate a statically significant improvement in visual acuity in GS010-treated eyes compared to sham-treated eyes.

During a meeting with a panel of key opinion leaders to discuss the clinical trial results, GenSight CEO Bernard Gilly expressed the company’s plans to bring the therapy to market as early as possible.

The company said the results from the phase 3 REVERSE trial showed continued efficacy of GS010 two years past injection, with best-corrected visual acuity sustaining a clinically meaningful improvement over baseline.

In the study, patients were dosed with the gene therapy in one eye and a sham treatment in the other. At Week 96, GS010-treated eyes showed a mean improvement of -0.308 LogMAR (a standardized scoring system of visual acuity) compared to baseline, equivalent to +15.4 ETDRS letters or 3 lines on the ETDRS vision chart. The ETDRS is a standardized measure of visual acuity that measures the ability of a patient to read letters on an eye chart.

As in previous readouts at Week 48 and Week 72, best-corrected visual acuity in sham-treated eyes evolved on a relatively parallel trajectory, achieving a mean improvement of -0.259 LogMAR over baseline, or a gain of +12.9 ETDRS letters equivalent, at Week 96.

Although lower in magnitude, the mean best-corrected visual acuity improvement of sham-treated eyes was not statistically significant from that of GS010-treated eyes.

Robert Sergott, director of the Wills Eye Hospital, said that the improvements in the sham-treated eyes suggest the gene therapy migrated from the treated to the untreated eye.

“The data show that both the treated and the sham eye improved in both high and low contrast, defying the accepted natural history of this disease and improving upon it, based upon the clinical experiences of generations of neuro-ophthalmologists,” said Sergott when the results were released. “The behavior of the untreated eye must also make us re-examine what we thought we knew as possibly dogma and be open to the idea that gene therapy delivered into one eye may be able to access the contralateral eye.”

Photo: Bernard Gilly, CEO of GenSight

Author: Rare Daily Staff

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