Available Treatments for IRDs

Available Treatments for IRDs

The development of effective therapies to prevent, cure or slow the rate of disease progression of inherited retinal disorders (IRDs) has been limited to date. However, recent progress in identifying the gene-causing mutations and characterising the disease mechanisms has provided opportunities for development of new therapeutic approaches.

At the current time, there are few approved and available treatments for people with IRDs. These currently consist of a visual prosthetic device (Argus® II Retinal Prosthesis System), and a gene therapy treatment (Luxturna) that was approved by the FDA in the United States in December 2017 and by the EMA in Europe in November 2018, for treatment of patients with IRDs caused by mutations in the RPE65 gene.

Argus® II Retinal Prosthesis System

The Argus® II Retinal Prosthesis System (“Argus II”; Second Sight Medical Products, Inc., CA, USA) is a retinal implant (artificial retina) designed to provide artificial vision to patients with near total vision loss due to outer retinal degenerative diseases, such as retinitis pigmentosa (RP). Argus II received CE-mark approval for commercial use in Europe in 2011, and Food and Drugs Administration approval in 2013 to treat adult patients with advanced retinitis pigmentosa in the United States. To date, Argus II been used by almost 300 people worldwide.

Argus II consists of a miniature video camera mounted on a pair of eye glasses. The video is sent to a small patient-worn computer containing a video-processing unit (VPU), where it is processed and transformed into instructions then sent back to the glasses via a cable. These instructions are transmitted wirelessly to an electrode array on the retinal implant on the surface of the retina, which emits small pulses of electricity. These electrical pulses bypass the damaged photoreceptors and stimulate the retina’s remaining cells, which transmit the visual information along the optic nerve to the brain. This process creates the perception of patterns of light which patients can learn to interpret as visual patterns.

Components of the Argus® II Retinal Prosthesis System

In clinical studies, Argus II has demonstrated improvements in visual function and performance on orientation and mobility tasks. Post-marketing studies to further evaluate its long-term safety and effectiveness are currently underway in Europe and the United States.

Luxturna (voretigene neparvovec) Gene Therapy

The RPE65 gene provides instructions for making a protein that is essential for normal vision function. The RPE65 protein is involved in a multi-step process called the visual cycle, which converts light entering the eye into electrical signals that are transmitted to the brain.

Mutations in the RPE65 gene lead to reduced or absent levels of RPE65 activity, blocking the visual cycle and resulting in impaired vision. People with biallelic RPE65 mutation-associated retinal dystrophy experience progressive deterioration of vision over time. Mutations in the RPE65 gene account for approximately 2% of cases of recessive RP and between 6 to 16% cases of Leber congenital amaurosis (LCA).

Luxturna works by delivering a normal copy of the RPE65 gene directly to retinal cells. These retinal cells then produce the normal RPE65 protein that converts light to an electrical signal in the retina to restore patient’s vision loss.

Luxturna is administered via subretinal injection in both eyes separately and on separate days. This procedure performed is a specialist eye surgeon. It is given as a one-time treatment.

The approval of Luxturna in the United States was based on the results of a clinical trial programme that enrolled a total 41 people between the ages of 4 and 44 years, all of whom had had confirmed biallelic RPE65 mutations. The effectiveness (efficacy) of the Luxturna was demonstrated by a Phase 3 clinical trial that enrolled 31 participants. The study found that at 1 year after the treatment, participants who received Luxturna had significantly improved light sensitivity, visual fields, and navigational ability under dim lighting conditions, compared with the control group (participants who were not treated Luxturna). In addition, no serious Luxturna-related adverse events were observed among individuals treated with Luxturna during the study.

In the United States, the manufacturers (Spark Therapeutics) have priced Luxturna at approximately $425,000 per one-off treatment (~$850,000 if a patient has the procedure on both eyes). They have also agreed an outcomes-based rebate arrangement with some healthcare insurers whereby the company will pay rebates if patient outcomes fail to meet a specified threshold, linking the payment for Luxturna to both short-term efficacy (30-90 days) and longer-term durability (30 months).

An article published in EyeNet Magazine® by the American Academy of Opthalmology® describes the impact that novel gene therapy Luxturna has had in the retina science research community, proving first-hand what can be achieved when we cooperate and unite to develop new therapeutics. Read the article here to hear another perspective on the importance of the Luxturna in bridging the gap to finding treatments for Inherited Retinal Diseases.