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GenSight Biologics Reports Long-Term Positive Safety and Visual Acuity Results at Week 96 in Phase I/II Study of GS010 for the Treatment of Leber’s Hereditary Optic Neuropathy

Sustained clinically significant improvement of visual acuity in LHON patients with less than 2 years of visual loss

Confirmation of the long-term safety profile of GS010

GenSight Biologics (Paris:SIGHT) (Euronext: SIGHT, ISIN: FR0013183985, PEA-PME eligible), a biopharma company that discovers and develops innovative gene therapies for neurodegenerative retinal diseases and diseases of the central nervous system, today reported additional promising clinical trial results with GS010 after 96 weeks of follow-up in its Phase I/II study. These results confirm the long-term positive sustained visual acuity gain after 2 years with a single intravitreal injection of GS010 in patients with Leber’s Hereditary Optic Neuropathy (LHON), especially in those with less than 2 years of disease onset.

Each cohort of three patients was administered an increasing dose of GS010 through a single intravitreal injection in the eye most severely affected by the disease. Recruitment was completed in April 2015 and long-term follow-up is ongoing. These patients had an average onset of disease of 6 years at the time of treatment. At baseline, both treated (TE) and untreated (UTE) eyes had an off-chart median visual acuity1.

At week 96 post-injection, in patients with an onset of vision loss of less than 2 years and relatively better vision (<2.79 LogMAR) at the time of treatment, a mean gain of +29 ETDRS letters (-0.57 LogMAR) was observed in TE compared to baseline, with a mean gain of +15 ETDRS letters (-0.30 LogMAR) in UTE, resulting in a difference of +14 ETDRS letters in favor of TE. This improvement is clinically significant, and the magnitude of improvement similar to the observed trend at week 48 and week 78.

The patient group with an onset of vision loss of 2 years or less and relatively better vision (<2.79 LogMAR) at the time of injection (n=5) demonstrated a treatment effect in favor of the treated eye of increasing magnitude from week 36 onwards with 60.0% of patients showing clinically significant ≥ 15 letters gain on EDTRS visual charts2. The characteristics of this patient group are similar to the baseline characteristics of LHON patients enrolled in ongoing Phase III REVERSE and RESCUE clinical trials3.

The mean change of visual acuity from baseline in TE of all patients (n=14) showed an improvement of +21 ETDRS letters (-0.41 LogMAR) and was statistically significant (p = 0.0159). There was no observed difference with the mean change from baseline in the UTE. There was a linear correlation between the TE and UTE in the change from baseline to week 96 that reached 0.67 and was highly significant (p = 0.0067). Based on all subjects except one, the improvement in UTE was only observed when there was an improvement in TE, which was significantly larger than the natural visual recovery4.

Lastly, the results confirmed the long-term good safety and tolerability of GS010 with no reported vision worsening or ocular sequelae, no serious treatment-emergent adverse events (TEAEs) nor systemic adverse events (AEs) related to study drug or procedure. As expected, mostly mild, well-tolerated, and completely reversible ocular AEs that were responsive to standard therapy occurred.

Bernard Gilly, CEO and co-founder of GenSight, commented, “We continue to see a sustained clinical benefit for patients in this long-term follow up after 2 years with a single injection, and this is very encouraging. Furthermore, this data continues to support the design of our two Phase III studies with GS010 for the treatment of Leber’s Hereditary Optic Neuropathy, which are currently ongoing in the U.S. and Europe, addressing patients with an early onset of vision loss. We are now less than a year away from Phase III efficacy data, and more than ever committed to find a cure for patients and their families affected by this devastating condition.”

Dr. Catherine Vignal, investigator of the study and Chief of the Department of Ophthalmology at the Rothschild Foundation Hospital in Paris, added, “The confirmatory safety and continued positive trends after 2 years of follow-up confirm significant hope for patients suffering from LHON. It is worth noting that the observed improvement in some of the untreated eyes was consistent with several prior studies in neuroretinal degenerative diseases. The insights gained from this and forthcoming data will be tremendously helpful as GenSight works to develop a therapy for this very severe disease with no existing curative treatment.”

The full data from the Phase I/II up to week 96 analyses is pending submission as a peer-reviewed manuscript.

GenSight Biologics is currently conducting two Phase III clinical studies (RESCUE and REVERSE) in Europe and the United States to assess the efficacy of GS010 in patients affected with LHON due to the ND4 mutation, with vision loss up to one year at the time of treatment. Recruitment of REVERSE was completed in February 2017, while RESCUE is expected to be completed by the end of July 2017. Topline results at 48 weeks of both studies are expected in the second and third quarters of 2018, respectively.


1 At baseline, treated worse-seeing eyes had a median visual acuity of 2.79 LogMAR (approximately equivalent to hand motion at 1m) and untreated better-seeing eyes had a median acuity of 2.01 LogMAR (approximately equivalent to counting fingers at 50cm).

2 Clinical significance being defined as a change from baseline of at least 0.3 LogMAR decrease (≥15 ETDRS letters gain).

3 One patient had an onset of vision loss of 9 months (eligible to REVERSE, 6 to 12 months), and 4 patients had an onset of vision loss > 1 year and < 2 years. None would have been eligible to RESCUE (<6 months).

4 Lam BL, Feuer WJ, Schiffman JC, et al. JAMA Ophthalmol. 2014 Apr 1;132(4):428-36.

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