Podcast recap: Daniel Chung on the evolution of retinal gene therapy

In the latest episode of The Genetics Podcast, we spoke with Dr. Daniel Chung, Chief Medical Officer at Beacon Therapeutics. The conversation focused on how retinal gene therapy has evolved since Luxturna, why progress has been slower than many expected, and what needs to change for the field to deliver repeatable late-stage successes in inherited retinal disease.

Daniel brings more than three decades of experience in ophthalmology and was deeply involved in the Luxturna program from early clinical development through approval. His perspective spans academic research, industry execution, and regulatory interaction.

Luxturna and the foundation of retinal gene therapy

Luxturna became the first FDA-approved in vivo gene therapy for a genetic disease in 2017. Daniel explains that its importance goes beyond treating RPE65-mediated disease.

The program established subretinal delivery as a viable and transferable surgical approach. It demonstrated a favorable safety profile for AAV vectors in the eye and highlighted the importance of vector optimization and manufacturing quality. It also showed that success in retinal gene therapy depends heavily on selecting endpoints that reflect meaningful functional change for patients.

Daniel discusses the development of the Multi-Luminance Mobility Test as a disease-specific endpoint designed for early-onset retinal degeneration where light sensitivity declines quickly. While effective for RPE65 disease, he emphasizes that this approach does not translate across all inherited retinal conditions.

Why progress after Luxturna has been slow

Despite dozens of ocular gene therapies entering clinical trials, Luxturna remains the only approved product to date. Daniel attributes this to a combination of scientific, regulatory, and operational challenges rather than a lack of innovation.

One central issue has been endpoint selection. Many inherited retinal diseases progress slowly, making it difficult to demonstrate meaningful change within typical trial timelines. Endpoints that are not well matched to disease biology can set an unworkably high bar, even for biologically active therapies.

Daniel also notes that investor and regulatory expectations have shifted. Programs increasingly need early clinical efficacy signals to sustain funding and advance into pivotal trials, raising the stakes for early development decisions.

Beacon Therapeutics and lessons applied to retinitis pigmentosa

Daniel joined Beacon Therapeutics to help advance a later-stage retinal gene therapy program and apply lessons learned from earlier efforts in the field. Beacon’s lead program targets RPGR for X-linked retinitis pigmentosa.

He explains how Beacon designed its pivotal trial based on prior clinical data and regulatory feedback, focusing on endpoints that reflect early functional loss in RPGR disease. These include low-luminance visual acuity and mean microperimetry sensitivity, both of which showed encouraging signals in phase 2 studies.

Beacon is preparing for a pivotal trial readout expected in late 2026. Daniel describes the emphasis on consistent surgical execution, standardized procedures across sites, and reducing variability that can obscure true treatment effects.

Genetic testing as a prerequisite for progress

Daniel strongly advocates for genetic testing across inherited retinal disease, including in gene-agnostic development programs. Knowing the underlying genetic cause informs prognosis, trial eligibility, and patient counseling.

He highlights the role of organizations such as Foundation Fighting Blindness in expanding access to testing and argues that genetic diagnosis should be treated as standard of care rather than an optional research step.

What will signal progress for the field

Looking ahead, Daniel suggests that progress in retinal gene therapy will depend on clearer regulatory alignment, better endpoint selection, and continued improvement in manufacturing and trial execution.

He believes the next set of pivotal trials will be important not because they promise dramatic shifts, but because they will show whether retinal gene therapy can be developed in a more consistent and repeatable way across different diseases.

Listen to the full episode below.