Reviewed by Jose-Alain Sahel, MD
An optogenetic treatment, GS030-MD (GenSight Biologics), combining gene therapy and a medical device, demonstrated a good safety profile in the Phase 1/2 PIONEER trial (NCT03326336) in patients with terminal retinitis pigmentosa (RP), according to José -Alain Sahel, MD.
RP, a genetic disease resulting from mutations in more than 100 genes, causes slowly progressive photoreceptor degeneration and blindness.
In the multicenter, open-label safety trial, the gene therapy vector delivered the light-sensitive protein, ChrimsonR, to participants’ retinal ganglion cells. The optoelectronic device contains glasses that encode the visual scene and project corresponding pulses of light onto the retina to activate the retinal ganglion cells.
The patients were divided into 3 cohorts of 3 patients each, who received increasing doses. In cohort 1, the dose was 5 × 1010 vg/eye; cohort 2, 1.5 × 1011 vg/eye; and cohort 3.5 × 1011 vg/eye; 1 intravitreal dose was injected into the eye with the worst visual acuity. An extension cohort receives the highest dose administered; participants are currently being registered.
All patients had end stage disease with visual acuity of finger counting or worse. Patients are followed for 5 years. The primary endpoint was safety at 1 year.
Intraocular inflammation developed in 5 (56%) patients, with 8 reported episodes resolving without sequalae with corticosteroid treatment. Anterior uveitis developed in 3 patients: 2 had received the low dose and 1 had received the medium dose.
One episode each of hyalitis with retrocorneal precipitates and anterior uveitis with retrocorneal precipitates developed in association with the high dose, Sahel reported. He is chairman of the Department of Ophthalmology at the University of Pittsburgh School of Medicine in Pennsylvania and a professor at the Sorbonne Université in Paris, France.
Two patients reported photosensitivity and 1 patient had an elevated IOP.
Two patients achieved significant improvement in vision over the course of 1 year. According to Sahel, the patients could hardly perceive light before treatment and after 1 year they could locate and count objects.
One of these patients, who had had RP for 40 years, 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.
Training with the device started 4 months after the injection. The light-stimulating glasses were well tolerated by the patients.
The PIONEER study was the first clinical trial for patients with RP to combine the simultaneous action of gene therapy and a medical device. It is a therapeutic approach that is independent of underlying genetic defects.
The researchers believed that the therapy was well tolerated up to 3 years after receiving the gene therapy. The preliminary efficacy assessment showed partial functional recovery in 2 patients.
“As we now see the benefits of this first-in-human therapeutic approach in more patients, we are optimizing the pacing system and filing patents for the expansion cohort. Optogenetics certainly holds great promise for our most affected patients,” concluded Sahel.
Jose-Alain Sahel, MD
Dr. Sahel is a founder of and an unpaid advisor to GenSight Biologics.