The potential of cell and gene therapy has been a subject that has been captivated medical professionals for decades, with this excitement growing even greater in recent years as the decades of theory and research have been put to the test in major trials across a slew of disciplines.

For a multitude of reasons, cell and gene therapies have found a home for themselves more quickly in some specialties than others. One of the specialties with a great degree of fervor for the subject has been ophthalmology. Despite this enthusiasm, the field has only witnessed a single gene therapy receive approval, with the US Food and Drug Administration’s approval of voretigene neparvovec-rzyl (Luxturna) for the treatment of patients with confirmed biallelic RPE65 mutation-associated retinal dystrophy.

However, new agents could soon join voretigene neparvovec-rzyl as cell and gene therapies boasting approvals for ophthalmic conditions. The community received deeper insight into a myriad of therapies in development at the42nd American Society of Retina Specialists (ASRS) Annual Scientific Meeting. As part of our coverage of the meeting, we are recapping our 5 most popular pieces of content from the meeting on the subject of cell and gene therapies.

ASRS 2024: Cell and Gene Therapies in Ophthalmology Recap

RESTORE: MCO-010 Significantly Improves Visual Acuity in Retinitis Pigmentosa

At ASRS 2024, Michael Singer, MD, of Medical Center Ophthalmology Associates, presented data from the phase 2b/3 RESTORE trial, which concluded high- and low-dose MCO-010 optogenetic therapy significantly improved BCVA in patients with retinitis pigmentosa. MCO-010 is a genetic mutation agnostic optogenetic therapy designed to transduce bipolar cells to express a photosensitive opsin protein and restore light sensitivity to the retina.

According to results, MCO-010 achieved both the primary and key secondary endpoints in RESTORE, with statistically significant improvement in BCVA for both doses at Week 52 and the high-dose group at Week 76. These clinically meaningful improvements in visual acuity were sustained at Week 100 for approximately 30% of MCO-010-treated patients.

OCU400 Shows Benefit for Retinitis Pigmentosa in Phase 1/2 Data

At ASRS 2024, Benjamin Bakall, MD, PhD, of Associated Retina Consultants presented data from a phase 1/2 clinical trial of OCU400, a novel therapeutic approach to reset the molecular clock by expression of the Nuclear Hormone Receptor, NR2E3, for the treatment of retinitis pigmentosa.

The multicenter, open-label clinical trial was designed as a 3+3 dose escalation and expansion study and enrolled participants with mutations in biallelic autosomal recessive NR2E3, autosomal dominant NR2E3, or autosomal dominant RHO. All participants received a single unilateral subretinal injection of OCU400 at 1 of 3 dosing levels: 5.0 x 109, 1.0 x 1010, or 5.0 x 1010 vg/eye. The ASRS presentation included data from 18 participants who had completed the 12-month follow-up visits.

Safety results of the trial indicated no serious adverse events (SAEs) correlated with OCU400 were identified in either the low- or medium-dose cohorts. Among those in the high-dose and open-enrollment cohorts, 2 participants experienced SAEs. One was deemed related to surgical technique and the other to OCU400 and surgical technique.

Efficacy data showed stabilization or improvement in 89% (n = 16 of 18) of participants in treated eyes, assessed through BCVA, LLVA, or MLMT scores compared with baseline. Specifically, 78% (n = 14 of 18) of participants experienced stabilization or improvement in baseline MLMT scores, with 80% (n = 8 of 10) of participants with RHO mutations experiencing improvement.

4D-150 Could Reduce Burden, Treatment Interval of Anti-VEGF Therapy

An interim analysis of the phase 2 PRISM trial detached the effects of 4DMT’s intravitreal dual-transgene payload inhibitor 4D-150 among a broad neovascular (wet) age-related macular degeneration (AMD) population.

A total of 45 patients were enrolled at 2 dose level arms of 4D-150, with 30 receiving a dose of 3E10 vg/eye and 15 receiving a dose of 1E10 vg/eye. Investigators noted patient characteristics were generally well-balanced, with the overall cohort having a mean CST of 329 μm and mean number of actual injections in the prior 12 months was 4.4.

At ASRS, data from a 24-week interim analysis of the trial suggested use of the 3E10 vg/eye dose, which is the planned phase 3 dose, offered robust anti-VEGF treatment reductions in the form of an 89% reduction in mean annualized injection rate and 77% of patients remaining injection free at 24 weeks.

At ASRS, we spoke to Raj Maturi, MD, about the results:

Pharmacodynamic Data Sheds Further Light on RGX-314

Data from a phase 2 pharmacodynamic study of ABBV-RGX-314 gene therapy were presented at ASRS 2024. An investigational single-administration gene therapy that delivers a transgene for a soluble anti-vascular endothelial growth factor (VEGF) Fab, the wet AMD therapy is in currently being examined in the phase 3ATMOSPHERE and ASCENT trials.

The phase 2 pharmacodynamic bridging study in wet AMD assessed the clinical performance between subretinal RGX-314 produced with REGENXBIO’s proprietary NAVXpress bioreactor platform process and an initial adherent cell culture manufacturing process used in the Phase 1/2a trial, which concluded subretinal delivery of investigational ABBV-RGX-314 gene therapy provided by the NAVXpress bioreactor platform was well-tolerated with a similar clinical profile to the adherent cell culture process.

The pharmacodynamic trial included 60 patients assigned to 6.4/1010 GC/eye or 1.3/1011 GC/eye, with half of the population receiving the bioreactor process and the other half receiving the adherent cell culture manufacturing process. The primary endpoint of interest was protein concentration of RGX-314 in the eye at month 6.

Results of the study indicated RGX-314 was well-tolerated across all cohorts. In total, 5 serious adverse events were reported, but none were believed to be related to the study drug. RGX-314 protein concentrations in the study eye were similar across 6 months in the high-dose (n = 30) and low-dose (n = 15) cohorts.

In addition, both study cohorts demonstrated stable-to-improved best-corrected visual acuity (BCVA) and central retinal thickness (CRT), and meaningful reductions in anti-VEGF burden. Many patients (67–77%) remained injection-free and there was a 68–86% reduction in the need for supplemental anti-VEGF therapy.

At ASRS, Edward Wood, MD, spoke to the editorial team of HCPLive Ophthalmology about the pharmacodynamic trial:

Pharmacodynamic Data Further Supports Ixo-vec in Wet AMD

Data from the LUNA trial presented at ASRS 2024 offered ophthalmologists and retina specialist even further insight into the efficacy and tolerability of ixoberogene soroparvovec (Ixo-vec) intravitreal gene therapy for wet AMD.

Ixo-vec, previously known as ADVM-02, has demonstrated vision preservation and sustained reduction in macular fluid through 3 years after a single intravitreal injection in the first-in-human trial, OPTIC. The ongoing multicenter, randomized, double-masked LUNA study evaluated the optimal dose of Ixo-vec combined with enhanced corticosteroid prophylactic regimens for wet AMD and included a prespecified 26-week interim analysis.

Trial participants were randomized between two Ixo-vec doses of 6 x 1010 and 2 x 1011 vg/eye and multiple prophylactic regimens, including local corticosteroids with and without oral prednisone. The trial’s primary endpoints were the incidence and severity of adverse events and the mean change in best-corrected visual acuity from baseline to week 52.

Results demonstrated a single Ixo-vec intravitreal injection led to a 90–95% reduction in annualized anti-VEGF injections and maintenance of visual and anatomic outcomes in treatment-experienced patients with wet AMD.

At ASRS, presenting investigator Charles C. Wykoff, MD, PhD, director of clinical research at Retina Consultants of Texas, sat down with the editorial team of HCPLive Ophthalmology to provide more perspective:


Relevant disclosures for Wood include Genentech, RegenXBio, Pharming, Allergan, and Iveric Bio. Relevant disclosures for Wykoff include Adverum Biotechnologies, Apellis, Genentech, Iveric, Regeneron, and others. Relevant disclosures for Maturi include Allergan, Genentech, Unity Biotechnology, and others.