Recent research and developments in gene therapy and cell therapy have shown therapeutic promise in a range of inherited retinal diseases (IRDs), many of which are currently incurable and lead to irreversible vision loss, delegates attending the EURETINA session were told.
Chaired by Bart Leroy and Isabelle Audo, the session was opened by Alberto Auricchio MD who discussed his research on expanding adeno-associated virus (AAV) transfer capacity in the retina. Although AAV vectors diffuse well in the subretinal space, their limited cargo capacity means they can usually only package a short DNA sequence and many IRDs require transfer of larger genes. Dr Auricchio and co-workers have been working on a dual vector approach, in which a transgene is split across two separate AAV vectors. The approach is currently being tested in indications such as Usher Syndrome and Stargardt disease.
Dominik Fischer MD, FEBO presented the latest data from the ongoing PERCEIVE study to establish the real-world safety and effectiveness of voretigene neparvovec (VN), the first approved ocular gene therapy for patients with RPE65-mediated inherited retinal dystrophy and sufficient viable retinal cells. “Based on this year 2 interim analysis, the PERCEIVE study demonstrates the safety and effectiveness of VN, which is consistent with those observed in the pivotal VN clinical trials,” he said.
Isabelle Audo MD, PhD discussed the rich promise of optogenetic therapy to potentially restore some visual function in blind patients with late-stage retinitis pigmentosa (RP). Optogenetic therapies combine cellular expression of light-sensitive opsins with light stimulation using a medical device. Dr Audo cited the report published in Nature Medicine in May 2021 detailing the partial recovery of visual function in a 58-year old patient who has been blind for 15 years and who was first diagnosed with RP 40 years ago. After optogenetics therapy, he could locate and count objects on a table and identify crosswalks in the street. Another optogenetic treatment, MCO-010 (Nanoscope) completed phase 1 trials in 11 patients with RP, which showed that the treatment was well-tolerated, with improved quality of life consistent with significant functional vision improvement in advanced RP patients. A phase 2 trial of MCO-010 with 27 participants with advanced RP is currently underway.
Paul Sieving MD, PhD, gave an update on intravitreal AAV-based gene therapies for X-linked retinoschisis (XLRS), an inherited retinal disorder that can cause early vision loss in males. He reported that a phase I/IIa clinical trial of a AAV8-RS1 gene therapy in which XLRS patients received a gene vector by intravitreal injection showed good tolerability and plausible biological activity. Ocular events included dose-related inflammation that resolved with topical and oral corticosteroids. Further trials of the therapy are planned, potentially with new delivery methods with novel capsids that penetrate the internal limiting membrane, he said.
Bart Leroy MD discussed the trial results of sepofarsen, an intravitreal RNA antisense oligonucleotide, for the treatment of CEP290-associated Leber congenital amaurosis (LCA10). The ILLUMINATE trial, at 14 sites in 9 countries, was a randomized, double-masked, sham-controlled, phase 3 study with 36 participants aged eight years or older with genetically confirmed LCA10. The trial did not meet the primary endpoint of best-corrected visual acuity (BCVA) at month 12 compared to sham control. However, when adjusting treated and sham eyes by subtracting effects of their corresponding control eye, a numeric treatment difference between sepofarsen and sham was observed. The overall safety profile of sepofarsen was also consistent with earlier trials. Despite the relatively promising results, Dr Leroy said that the company ProQr had decided not to pursue further trials of sepofarsen, illustrating the difficulty of taking gene therapy treatments to market.
The final two presentations saw Isabelle Audo discuss the early data on ultevursen, a new RNA interference therapy for USH2A, a progressive disease leading to blindness, and Mark Pennesi MD who gave an update on CRISPR/Cas9 therapy for the treatment of CEP-290 related retinal degeneration.
All registered attendees will be able to view this session via playback on the virtual platform.