Qualifications for Retinitis Pigmentosa and Leber Congenital Amaurosis Patients for Adeno-Associated Viral Gene-Replacement Therapy Clinical Trials

Abstract

Introduction: This study identifies Retinitis Pigmentosa (RP) and Leber Congenital Amaurosis (LCA) patients at an Inherited Retinal Disease (IRD) clinic that qualify for ongoing or FDA-approved Adeno-Associated Virus (AAV) gene-replacement therapies. The goal is to demonstrate the benefits of genetic testing at the initial evaluation. Method: A database for RP and LCA patients was curated and clinicaltrials.gov was used to search all ongoing or approved gene-replacement therapies between 1 January 2022 – 1 January 2023. Patients were evaluated for qualification based on the inclusion/exclusion criteria set by each trial. Results: 199 RP and 31 LCA patients were included in the study. Our team identified six AAV gene-replacement therapy clinical trials and the FDA-approved Luxturna®. One hundred fifty-five patients underwent genetic testing and 89 patients had a pathogenic variant identified. A total of 15 patients qualified for one of the proposed trials. Three patients had a biallelic RPE65 mutation and two of them qualified for Luxturna®. All 11 patients with an RPGR mutation qualified for one of the three clinical trials that focused on this gene. Three patients had a c.2991+1655A>G mutation in CEP290 and two of them qualified one of two clinical trials for this gene. Conclusion: Overall, ~10% of patients who had genetic testing qualified for one of the reviewed therapies. A total of 15 patients qualified for an AAV gene-replacement therapy. This study highlights the importance of promoting genetic testing for IRD patients, the need for earlier disease evaluation and the value of continual monitoring of disease progression.