GenSight Biologics 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 (LHON) commenced between 6 and 12 months prior to study treatment.
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.
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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).
“The level of sustained improvement in both visual acuity and low-contrast sensitivity, and the sustained preservation of retinal ganglion cells on OCT, at this stage of disease progression is very encouraging, and is a departure from what has been observed and reported on the natural history of LHON,” said Dr. Mark L. Moster, Neuro-Ophthalmology, Wills Eye Hospital, Professor of Neurology and Ophthalmology at Thomas Jefferson University, Philadelphia, PA, and Principal Investigator in REVERSE and RESCUE trials.”