Revolutionizing Wet AMD Treatment: The Rise of Suprachoroidal Gene Therapy

The treatment landscape for wet age-related macular degeneration (AMD) is evolving rapidly with the emergence of gene therapy. Among the innovative strategies gaining attention is suprachoroidal administration, a technique that delivers gene therapy directly to the retina through the potential space between the choroid and sclera. This approach aims to provide sustained therapeutic effects, potentially reducing the need for frequent intravitreal injections that burden patients and healthcare systems.

Current Treatment Challenges and the Promise of Gene Therapy

Intravitreal anti-VEGF injections remain the standard of care for wet AMD, yet the necessity for monthly or bimonthly administration presents significant adherence and logistical challenges. Gene therapy offers the potential to transform treatment paradigms by providing durable VEGF inhibition, minimizing injection frequency and improving long-term disease control.

Suprachoroidal Administration: A Targeted Approach

Suprachoroidal injection allows precise delivery of therapeutic agents to the posterior segment of the eye, where wet AMD pathology occurs, while limiting exposure to anterior structures. This method may reduce the risk of inflammation and offer more uniform retinal drug distribution compared to intravitreal delivery.

KH658 and the VAN-2401 Phase 1 Trial

A pivotal development in this space is the KH658 gene therapy, currently under investigation in the VAN-2401 Phase 1 clinical trial. Jointly launched by Chengdu Origen Biotechnology and Vanotech, this multicenter, open-label, dose-escalation study recently dosed its first patient. KH658 utilizes a recombinant adeno-associated virus (AAV) vector encoding a human VEGF receptor fusion protein, engineered to continuously suppress VEGF activity at the retinal level.

The goal is to alleviate the treatment burden by enabling long-lasting anti-VEGF expression from a single suprachoroidal injection. Preclinical findings support KH658’s capacity for sustained protein production and VEGF inhibition in the retina.

Early Insights and Future Directions

Early safety and tolerability data from the VAN-2401 trial will guide future development, including dosing strategies and risk–benefit assessments. Key metrics will include visual acuity outcomes, retinal anatomy changes, and immune response monitoring to define long-term efficacy.

As gene therapy technologies mature, suprachoroidal administration may emerge as a cornerstone in the treatment of retinal diseases. The success of KH658 and similar programs could lead to reduced treatment burden, improved adherence, and optimized clinical resource use.

Suprachoroidal gene therapy represents a promising frontier in ophthalmology, offering a novel method to manage wet AMD with enhanced precision and durability. Continued multidisciplinary collaboration will be essential to refine injection techniques, manage potential complications, and integrate this approach into routine clinical care.