Luxturna: First FDA-Approved Gene Therapy for Inherited Retinal Disease (Subretinal Injection)

Inherited retinal diseases (IRDs) are a group of rare genetic conditions that can lead to severe cases of vision loss. Particularly, Lebel congenital amaurosis (LCA), is a severe form of IRD that typically begins in early childhood. A specific subtype of LCA is caused by certain mutations in the RPE65 gene, leading to defects in the eye’s ability to detect light. Until recently, no effective treatments existed to combat this condition. However, in 2017, the U.S. Food and Drug Administration (FDA) approved Luxturna (voretigene neparvovec-ryzl), the first gene therapy for an inherited retinal disease. While there are many mutations that can occur within the RPE65 gene, Luxturna works against biallelic mutations or mutations where both copies of the gene are altered. These mutations prevent the retina from being able to properly process light and can lead to severe visual impairment. Luxturna fights this by developing a functional copy of the RPE65 gene directly into the patient’s retinal cells through adeno-associated virus (AAV), a harmless virus that acts as a vector. This procedure occurs through subretinal injection, which involves the gene therapy being directly injected beneath the retina. This allows the new gene copy to reach the target cells and begin producing the correct protein that the eye needs for proper vision. Though the surgery is intricate and requires specialists, it is considered to be minimally invasive compared to traditional eye surgeries.

Over recent years, clinical trials have demonstrated that Luxturna can lead to significant improvements in functional vision for people with this subtype of LCA. According to many studies, many patients saw substantial progress in their ability to navigate obstacle courses in dim light after receiving treatment. Additionally, patients also experienced enhanced visual accuracy and light sensitivity. While Luxturna has definitely created a groundbreaking development in genomic medicine and ophthalmology, it still doesn’t present a complete cure to the problem. The treatment is still being tested for long-term effectiveness and ability to completely restore vision rather than only improve it. Additionally, the treatment is widely unaccessible to large populations, specifically due to its price of around $850,000 for both eyes. Despite these limitations, Luxturna still marks a turning point in the treatment of genetic retinal disorders. It has also proved that gene therapy can be used to directly target the root cause of a disease rather than only mitigate its symptoms. The success that this treatment has seen thus far has encouraged researchers to explore genetic therapies for other inherited diseases, offering the potential to treat patients with previously untreatable disorders.

Written by Anonymous at Incisionary

“FDA Approves Novel Gene Therapy to Treat Patients with a Rare Form of Inherited Vision Loss.” U.S. Food and Drug Administration, 19 Dec. 2017, www.fda.gov/news-events/press-announcements/fda-approves-novel-gene-therapy-treat-patients-rare-form-inherited-vision-loss.

“Luxturna.” Spark Therapeutics, www.luxturna.com.

Reichel, F. F. L. (2021). An optimized treatment protocol for subretinal injections limits intravitreal vector distribution. Ophthalmology Science, 1(4), 100048. https://doi.org/10.1016/j.xops.2021.100048

Russell, Stephen, et al. “Efficacy and safety of voretigene neparvovec (AAV2-hRPE65v2) in patients with RPE65-mediated inherited retinal dystrophy: a randomised, controlled, open-label, phase 3 trial.” The Lancet, vol. 390, no. 10097, 2017, pp. 849–860.