Optogenetics in the clinic: safety and efficacy updates on the phase 1/2 clinical trial PIONEER

Abstract

Purpose : Evaluate the GS030 optogenetic therapy in subjects with end-stage non-syndromic retinitis pigmentosa.

Methods : The GS030 optogenetic therapy combines an intravitreal injection of gene therapy with the use of a medical device. The GS030 gene therapy vector expresses channelrhodopsin ChrimsonR-tdTomato in retinal ganglion cells. The light-stimulating goggles encode the visual scene and project corresponding light pulses to activate the retinal ganglion cells. PIONEER is an international open-label dose-escalation clinical study of GS030 for the treatment of late-stage retinitis pigmentosa.

Results : 9 patients were injected with increasing doses of gene therapy: 3 received 5E10 viral genomes (vg)/eye, 3 received 1.5E11 vg/eye, and 3 received 5E11 vg/eye. Started 8 weeks after injection, the use of light-stimulating goggles was well tolerated. The main ocular adverse event related to gene therapy was mild intraocular inflammation responsive to corticosteroid treatment. Following systematic visual training with the goggles, two patients were able to locate and touch small objects on a table. One of these 2 patients underwent EEG recording during a visual test, which showed vision-related cortical activity.

Conclusions : GS030 demonstrates a good safety profile up to 2.5 years after vector administration, and preliminary efficacy assessment shows partial functional recovery in two patients.

This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.