Frequency and Pattern of Gene Therapy Clinical Trials for Inherited Retinal Diseases

Abstract

This study describes worldwide gene therapy clinical trials aimed at treating inherited retinal diseases (IRD). The information was collected through 15 different international registries including clinicaltrials.gov . There have been 101 gene therapy clinical trials targeting IRD up until the end of 2022. Seventy-seven trials employed gene augmentation using viral vectors; other approaches included inhibitory RNA (9), encapsulated cell technology (6), systemic approach (1), and observational trials (8). The most common clinical trial phase was phase 1/2 (46), followed by phase 3 (12). One trial led to an FDA-approved treatment. Sixty-nine trials were conducted in a single country, and 32 trials were multinational; The USA had the highest share in both categories. Retinitis pigmentosa was the most common disease targeted (39), followed by RPE65-mediated retinal dystrophy (13), Leber hereditary optic neuropathy (13), choroideremia (10 and achromatopsia (8), Leber congenital amaurosis (4), X-linked retinoschisis (4), Stargardt disease (4), Bietti's crystalline dystrophy (2), autosomal dominant optic atrophy (1), and Gyrate atrophy (1). For gene augmentation trials, adeno-associated virus was the most commonly used viral vector (70 trials-90%).

Keywords: Clinical trials; Gene augmentation; Gene therapy; Inherited retinal degeneration; Leber congenital amaurosis; Leber hereditary optic neuropathy; Optogenetics; Retinitis pigmentosa; Viral vectors.