Abstract
Purpose :
This study identifies Retinitis Pigmentosa (RP) and Leber Congenital Amaurosis (LCA) patients at an inherited retinal disease (IRD) clinic that qualify for ongoing clinical trials or FDA-approved adeno-associated virus (AAV) gene-replacement therapies. The goal is to evaluate the benefit of genetic testing at the initial evaluation of IRD patients.
Methods :
A REDCap database was created to record genetic testing results for RP and LCA patients that were seen between May 1, 2015 – Aug 5, 2022. A search through clinicaltrials.gov to identified all ongoing AAV gene-replacement therapy clinical trials. The FDA-approved AAV therapy for LCA, vortigene neparvovec, was also included. Patients who had a diagnostic pathogenic variant were evaluated for qualification based on the inclusion/exclusion criteria set by each trial.
Results :
199 patients with RP and 31 patients with LCA were included. A total of seven AAV gene-replacement therapy clinical trials were identified. 155 patients underwent genetic testing: 89 patients had a diagnostic variant identified. A total of 18 patients (12% of those who underwent genetic testing) qualified for an AAV gene-replacement therapy. Three patients had a biallelic RPE-65 mutation: two qualified for vortigene neparvovec; the other was excluded due to advanced disease. All 11 patients with an RPGR mutation qualified for at least one of three trials that focused on this gene (NCT04671433, NCT04850118, NCT04517149). Three patients had a c.2991+1655A>G mutation in CEP290: two met qualifications for at least one of two available trials (NCT04855045, NCT03872479); one was excluded from both due to advanced disease. The final clinical trial (NCT03326336) focused on non-syndromic patients, and three patients qualified. Common exclusions for this trial included lack of disease severity, visual acuity, age outside of the required range, or insufficient diagnostic testing. Overall, ~12% of patients who had genetic testing qualified for one of the reviewed therapies.
Conclusions :
18 (~12%) patients who had genetic testing qualified for an AAV gene-replacement therapy. This study displays the increasing availability of genet therapy for patients with RP and LCA. It shows the importance of promoting genetic testing for IRD patients, the need for earlier disease evaluation, and the benefit of continual monitoring of disease progression for patients with an IRD.
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.