Eye on the Horizon: Gene Therapy

Gene therapy represents a unique method for how ophthalmologists might treat – as well as prevent – inherited retinal diseases (IRDs) and other vision disorders such as glaucoma and corneal neovascularization. But as the literature attests, currently the retina is where gene therapies might prove most beneficial. Indeed, as Selina Drag et al. note in their 2023 IOVS study, the light-sensitive layer of tissue “holds the distinction as the first tissue targeted by an approved gene therapy for inherited disorders in the United States” (1).

“The first ophthalmic gene therapy was approved by the FDA in 2017,” Vice President of Emerging Therapies at Cardinal Health, Fran Gregory, told The Ophthalmologist. Gregory was referring to the approval of Luxturna (voretigene neparvovec-rzyl), a therapy used to treat retinal dystrophy.

Since the 2017 FDA approval of Luxturna, various companies have sought to make further headway into the ophthalmic gene therapy space. These include innovative candidates such as GenSight Biologics’ light-stimulating goggles (GS030-MD), which, when combined with its AAV2-based gene therapy (GS030-DP), aim at enhancing visual restoration in end-stage retinitis pigmentosa (RP) patients. Then there is Adverum’s clinical-stage gene therapy, Ixoberogene soroparvovec (Ixo-vec, formerly referred to as ADVM-022), which is currently in phase II trials for wet age-related macular degeneration (AMD).

SparingVision – a biotechnology company based in Paris – is working on SPVN06, a gene therapy treatment with mid-stage RP as its primary disease target. The FDA cleared SPVN06's Investigational New Drug application (IND) in December 2022.

SparingVision has stated its gene therapy candidate could potentially address over 80 genetic mutations of RP;  the company also announced its intentions to extend trials of SPVN06 to geographic atrophy (GA) (2). “PRODYGY is the phase I/II clinical trial of SPVN06 in patients with moderate-to-severe RP,” says Stéphane Boissel, President and CEO of SparingVision. “The trial has since completed step one of patient recruitment. We are now preparing transition to the controlled, randomized extension phase of the trial aimed to take place in Q4 2024.”

“SPVN06 aims to slow or stop cone photoreceptor degeneration, regardless of the disorder’s genetic cause.This not only allows reaching a larger cohort of RP patients… [but also] offers a larger window of intervention over the course of the disease, as cone photoreceptors degenerate later than rod photoreceptors,” explains Boissel. “This approach can also be expanded beyond inherited retinal diseases, to other more prevalent conditions such as dry age-related macular degeneration (AMD) or geographic atrophy (GA), which are also linked to cone photoreceptor degeneration.”

Aside from Luxturna, no other gene therapies for ocular conditions have yet received FDA backing. However, the 2017 approval of the RPE65 gene mutation treatment has motivated other companies, leading to an increase over the last few years in clinical trials exploring gene therapy treatments for both inherited retinal diseases and non-hereditary ocular conditions. As Fran Gregory noted at the beginning of 2024, “With at least 25 treatments in phase I-III clinical trials, the advanced medicine pipeline is full of potential treatments for ocular conditions. The excitement for gene therapy is palpable, and for patients with genetic or inherited ocular conditions who have never before had treatment options, the future is promising.”

“The ocular field has seen incredible progress with genomic medicines in recent years, notably with the approval of Luxturna, but single-gene correction or single technology approaches are not enough,” Boissel adds. “We firmly believe that to transform the treatment of retinal disease, you need a multi-technology approach. At SparingVision, we are pioneering the treatment of blinding retinal diseases through a suite of gene-agnostic gene therapies, as well CRISPR-based products, with a view to providing treatment to large patient populations.”