Gene Therapy Trial for Mitochondrial Disease of Retina Found Safe, Can Continue
An independent Data Safety Monitoring Board (DSMB) has found GS030, GenSight Biologics’ candidate gene therapy for retinitis pigmentosa, safe and recommended the company’s PIONEER trial continue as planned.
PIONEER (NCT03326336) is a Phase 1/2 trial currently investigating the safety and tolerability of increasing doses of GS030 in up to 18 people with retinitis pigmentosa. The trial is ongoing at three centers in the U.S., U.K., and France.
Six patients have been enrolled and treated to date, but further trial recruitment is on temporary hold due to the COVID-19 pandemic, GenSight announced in a press release. Corticosteroids used before and after the gene therapy to minimize an inflammatory response to treatment puts patients at a higher risk for this coronavirus.
The company hopes to resume enrollment soon, depending on “the public health situation,” and to release early findings in these first two groups of treated patients. However, GenSight added that the pandemic could affect these plans.
Retinitis pigmentosa comprises a large group of inherited disorders that lead to the progressive degeneration of the retina, ultimately causing blindness. The retina, located at the back of the eye, contains several layers of light-sensitive cells that pick up and send visual signals to the brain, allowing a person to see.
This disorder can be caused by mutations in different genes, including mitochondrial genes, making some of its forms a type of mitochondrial disease.
GS030 is an investigational treatment based on GenSight’s new optogenetics technology. It uses gene therapy to introduce a gene providing instructions for the production of a light-sensitive protein into retinal ganglion cells, which form one of the layers of the retina.
By forcing these cells to produce this light-sensitive protein, GS030 restores their ability to respond to light signals, which had been compromised by the loss of photoreceptor cells found in other layers of the retina, the company reports.
GS030 is administered by an intravitreal (inside the eye) injection. Then, in order to stimulate ganglion cells with light signals and improve eyesight, patients wear a special optronic device that sends signals to activate the light-sensing proteins.
Two of three, dose-escalating groups of patients in PIONEER have been treated to date. People in each group (three patients per cohort) are given a single intravitreal injection of GS030 in their most affected eye, followed by repeated light stimulation with the wearable optronic device.
Once dosing is done in these three groups — all in people with end-stage disease and no or very poor light perception vision — an extension cohort of three to nine patients will be given the treatment’s maximum tolerated dose. Patients in the extension groups will be those with visual acuity that allows them to see hand motion or count fingers.
The independent DSMB confirmed no findings of safety issues in the second group of patients treated with GS030 at a dose of 1.5e11 viral genomes. The three patients in the awaited third initial group will be treated at high dose, 5e11 viral genomes (vg).
“We are pleased to be able to move forward with our second program GS030, which has now treated 6 patients,” Magali Taiel, MD, chief medical officer of GenSight Biologics, said in the release.
“We look forward to confirming the safety of GS030 at the highest dose and to demonstrate efficacy by showing signs of functional vision recovery in advanced stage RP patients,” Taiel said.
The six treated patients are being monitored remotely for safety reasons.