Combining gene therapy and medical device makes progress in RP

Reviewed by José-Alain Sahel, MD.

An optogenetic treatment, GS030-MD (GenSight Biologics), which combines gene therapy and a medical device, led to a phase 1/2 PIONEER trial (NCT03326336) for patients with end-stage retinitis pigmentosa (RP). Demonstrated a good safety profile. To José-Alain Sahel, MD.

RP, a genetic disease resulting from mutations in more than 100 genes, causes progressive photoreceptor degeneration and blindness.

In a multicenter, open-label safety study, the gene therapy vector delivered the light-sensitive protein, ChrimsonR, to participants’ retinal ganglion cells. The optoelectronic device includes glasses that encode the visual scene and project relevant light pulses onto the retina to activate retinal ganglion cells.

Patients were divided into 3 groups of 3 patients, each receiving escalating doses. In cohort 1, the dose was 5×1010 vg/ey; cohort 2, 1.5 × 1011 vg/ey; and cohort 3, 5 × 1011 vg/ey; 1 intravitreal dose was injected into the eye with impaired vision. An extended group will be given the highest dose. Participants are currently being enrolled.

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

Device performance

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

Sahil reported that one episode of hyalitis with retrocorneal precipitates and posterior uveitis with retrocorneal precipitates developed in association with high doses. He is chairman of the Department of Ophthalmology at the University of Pittsburgh School of Medicine in Pennsylvania and a professor at the Sorbonne University in Paris, France.

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Two patients reported sensitivity to light, and 1 patient had increased IOP.

Two patients achieved significant improvement in vision at 1 year. According to Sahil, patients could barely sense light before treatment and were able to find and count objects at 1 year of age.

One of these patients, with a 40-year history of RP, responded to the lowest of the 3 doses. Another patient had RP for 20 years and responded to moderate doses of gene therapy.

Training with the device began 4 months after injection. Mild stimulation glasses were well tolerated by patients.

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The PIONEER study was the first clinical trial for RP patients to use gene therapy and a medical device simultaneously. It is a treatment method independent of underlying genetic defects.

The investigators looked at well-tolerated therapy up to 3 years after gene therapy administration. Preliminary efficacy evaluation showed partial functional recovery in 2 patients.

“While we are now observing the benefits of this first-in-human therapeutic approach in more patients, we are improving the stimulation system and filing patents for an expanded cohort. Optogenetics is certainly our holds strong promise for the most affected patients,” concludes Sahil.

José-Alain Sahel, MD

Email: [email protected]

Dr. Sahil is the founder and unpaid consultant for GenSight Biologics.


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