For approximately 1 million Americans living with geographic atrophy (GA), currently available treatments can slow disease progression but cannot restore vision that has already been lost. Research presented at the 130th annual meeting of the American Academy of Ophthalmology (AAO) suggests an experimental gene therapy could offer a different approach. Investigators reported that a single injection of sonpiretigene isteparvovec, known as son-vec (Nanoscope Therapeutics), improved vision in patients with Stargardt disease and demonstrated encouraging activity in a nonhuman primate model designed to mimic GA, according to research being presented at AAO news release.  

The findings have supported plans to move the therapy into a randomized phase 2 trial in patients with dry AMD without first conducting a separate phase 1 study in this population, according to the researchers.

“There are currently FDA-approved treatments to slow down geographic atrophy progression, but no treatments are currently available to improve vision,” David S. Boyer, MD, lead investigator of the study, said in a statement. “Having a one-time injection, which appears safe, that may improve vision for my patients was a great reason to do the study.”

Using surviving retinal cells to respond to light

Son-vec uses an optogenetic approach intended to restore visual function after photoreceptors have been lost.

Photoreceptors—the rods and cones of the retina—convert light into electrical signals that ultimately allow the brain to produce visual images. Their progressive loss is a central feature of several retinal degenerative diseases, including GA. Rather than attempting to preserve or replace damaged photoreceptors, son-vec delivers a gene to bipolar cells, retinal neurons that normally transmit signals from photoreceptors and can remain intact after photoreceptor loss.

The therapy causes these cells to express a light-sensitive protein known as an opsin. This is intended to make the surviving bipolar cells directly responsive to light, effectively recruiting another part of the retinal circuitry to compensate for lost photoreceptor function.

Son-vec is administered as a single intravitreal injection.

Phase 2 data show visual gains in Stargardt disease

The findings presented at AAO included results from an open-label, multicenter phase 2 trial involving patients with Stargardt disease. Patients received a single injection of son-vec and entered the study with visual acuity of 20/200 or worse.

Among patients whose atrophy was confined to the macula, investigators reported an average improvement of 12 letters on a standard eye chart, representing a gain of more than 2 lines of vision.

The treatment was reported to be well tolerated, with no serious adverse events observed.

Researchers also presented findings from a dose-ranging study in nonhuman primates with laser-induced retinal damage designed to model GA. The study demonstrated expression of the therapy's protein in retinal neurons. Treated eyes also demonstrated significantly stronger electrical responses on multifocal electroretinography, which measures localized retinal responses to light, according to the investigators.

Son-vec has additionally been evaluated in patients with retinitis pigmentosa, another inherited retinal disorder involving photoreceptor degeneration, with improvements reported in some measures of visual function.

Despite the encouraging findings, the researchers emphasized that the human efficacy data presented to date are from patients with Stargardt disease rather than patients with GA secondary to AMD.

The Stargardt study was also open-label, meaning investigators and participants knew that treatment had been administered. A randomized controlled study in patients with GA will therefore be important for determining whether the findings translate to the larger population of patients with dry AMD.

Randomized geographic atrophy trial planned

Investigators are now preparing to evaluate son-vec in a randomized phase 2 trial involving patients with GA. If the results support continued development, Dr. Boyer said the next goal would be to conduct phase 2b/3a trials to confirm the findings and support a potential application for FDA approval.

For ophthalmologists treating patients with advanced dry AMD, Dr. Boyer characterized the early findings as a reason for cautious optimism.

“There may be a treatment for patients with visual loss secondary to geographic atrophy in the future that hopefully will result in visual gains,” he said.