Optogenetic treatment offers hope for patients with end-stage RP

Patients are currently being enrolled in the extension cohort in which the highest dose will be administered.

Reviewed by Jose-Alain Sahel, MD

An optogenetic treatment, GS030-MD (GenSight Biologics), comprised of a gene therapy and a medical device, demonstrated a good safety profile in the phase 1/2 PIONEER Clinical Trial including patients with end-stage retinitis pigmentosa (RP), according to Jose-Alain Sahel, MD, from the Sorbonne Université, Institut National de la Santé de la Recherche Medicale, Centre National de la Recherche Scientifique, Institut de la Vision, Paris, and Department of Ophthalmology, The University of Pittsburgh School of Medicine.

RP, a blinding genetic disease that results from mutations in more than 100 genes, causes slowly progressive photoreceptor degeneration and blindness.

In this multicenter, phase 1/2 open-label safety study, the gene therapy vector delivered the light-sensitive protein, ChrimsonR, to the retinal ganglion cells. The optoelectronic device includes goggles that encode the visual scene and project corresponding light pulses onto the retina to activate the retinal ganglion cells.

The patients were divided into 3 cohorts of 3 patients each who received escalating doses and an extension cohort in which the highest dose is administered. In cohort 1, the dose was 5 x 1010 vg/eye; cohort 2, 1.5 x 1011 vg/eye; and cohort 3, 5 x 1011 vg/eye; 1 intravitreal dose was injection into the eye with the worse vision.

All patients had end-stage disease with visual acuity of counting fingers or worse. Patients will be followed for 5 years. The primary endpoint was the safety at 1 year.

Device performance

Intraocular inflammation developed in 5 (56%) patients, with 8 such episodes reported that resolved without sequalae with corticosteroid treatment. Anterior uveitis developed in 3 patients, 2 receiving the low dose and 1 receiving the medium dose.

One episode each of hyalitis with retrocorneal precipitates and anterior uveitis with retrocorneal precipitates developed in association with the high dose, Dr. Sahel reported.

Two patients reported light sensitivity and 1 patient had increased intraocular pressure.

Two patients achieved a significant improvement in vision over the course of 1 year. The patients, according to Sahel, were barely able to perceive light before treatment and at 1 year were able to locate and count objects.

One of these patients who had a 40-year history of RP, responded to the lowest of the 3 doses. A second patient had RP for 20 years and responded to the intermediate dose of gene therapy.

The training with the device began 4 months after the injection. The light-stimulating goggles were well tolerated by the patients.

The PIONEER study was the first clinical trial for patients with RP that combined the simultaneous action of gene therapy and a medical device, which is a therapeutic approach that is independent of underlying genetic defects.

The investigators considered the therapy to be well tolerated out to 3 years after the gene therapy was administered. The preliminary efficacy assessment showed partial functional recovery in 2 patients.

Patients are currently being enrolled in the extension cohort in which the highest dose will be administered.

“While we are now observing the benefits of this first-in-human therapeutic approach in more patients, we are optimizing the stimulation system and enrolling patents for the extension cohort. Optogenetics certainly holds strong promises for our most affected patients,” Dr. Sahel concluded.

Jose A. Sahel, MD

E: sahelja@upmc.edu

Dr. Sahel is a founder and unpaid consultant to GenSight Biologics.