EyeWorld India December 2020 Issue

NEWS & OPINION EWAP DECEMBER 2020 59 lighting conditions. Another new paradigm was subretinal surgical administration; when Luxturna became available, Dr. Ciulla said ocular gene therapy treatment centers had to be established with staff who were trained to administer the therapy. A third new paradigm involved reimbursement for potential one-time therapies. Spark Therapeutics, Dr. Ciulla said, worked to help develop different payment models for the drug, as the current healthcare system is not equipped to properly value new therapies that yield long-lasting benefits in one administration. Because most of the research toward gene therapies is for rare, inherited disorders, such as RPE65 mutation, Dr. Sohn noted that the therapy is often expensive. “The price of the medicine is a challenge for companies to continue doing research or to get approval because of the cost they have to project in terms of charging private insurance carriers and the government,” said Dr. Sohn, a clinical investigator for the Phase 2/3 Luxturna trials. However, he went on to describe the long- term economic benefits to the individual, family, and ultimately the healthcare system when these therapies are administered. What’s in the pipeline? There are several companies working on gene therapies for recessive disorders. Dr. Ciulla listed achromatopsia (AGTC, MeiraGTx), Stargardt Chan Choi Mun, MD Senior Consultant, Singapore National Eye Centre 11 Third Hospital Avenue, Singapore 168751 chan.choi.mun@singhealth.com.sg ASIA-PACIFIC PERSPECTIVES This was an excellent summary on the state of gene therapy in ophthalmology. Can it be just “one and done” with Luxturna? From an Asian perspective, while it is encouraging to note that local regulatory approval for Luxturna may be obtained starting from the last quarter of 2021, I would caution that it may be premature to say that Luxturna is a “one and done” treatment. Granted that the 4-year follow-up of the phase 3 voretigene neparvovec (AAV2-hRPE65v2) trial in RPE65-associated Leber congenital amaurosis (LCA) showed that functional vision was stable in 24 of 28 patients from 1 year post treatment through to 3–4 years of follow-up, this is a small group and it is early days yet, especially since the mean age group of those treated was 14.7 years. Prudence is essential when counseling our patients about potential gene therapies, as many believe gene therapy is a miracle cure. For example, Luxturna therapy restores navigational vision. Patients do not regain vision good enough for reading or computer work. When I tell my patients this, they are disappointed and surprised. Genetic testing as a new standard of care Something else to highlight is the importance of genetic testing. Now that an FDA-approved treatment is available for RPE65-associated retinal degeneration, genetic testing for individuals with a diagnosis of LCA or early onset retinitis pigmentosa (RP) should be mandatory. Likewise, it is important to perform genetic testing on patients with a clinical diagnosis of any inherited retinal disease (IRD) which is currently undergoing evaluation for gene therapy in a phase 1/2 clinical trial in order to determine their candidacy for those trials. Many also advocate genetic testing for family planning if possible autosomal dominant or X-linked disease is suspected. Genetic testing in most Asian countries is for the most part fully funded by the individual, unlike in Western countries where one might be able to claim insurance for it. This is an area where governments in Asia would potentially need to step up. Comprehensive pre- and post-test genetic counseling is also critical so patients understand the implications of their results. When counseling patients, it is paramount that we rein in expectations, not just in terms of how much visual improvement gene treatments can offer, but also how soon they can obtain regulatory approval and be available. Lastly, we must also caution patients who may be too eager to embrace any new unsubstantiated gene therapy claims. In summary, gene therapy is personalized medicine, bringing with it the possibility of having an individual’s unique genetic mutation corrected. Gene therapy in the eye potentially holds much promise for patients that previously were told their vision would only worsen with time. However, before it can be offered, clinical grade genetic testing needs to be more widely performed. As clinicians, we also need to temper our patients’ expectations, not only in terms of what the outcome of gene therapy would be, but also in terms of how soon it can meet regulatory approval and be available for treatment. Editors’ note: Dr. Chan declared no conflicting interests.