Chengdu Origen Biotechnology Co., Ltd. and Vanotech Ltd. announced today that the first patient has been dosed in their VAN-2401 Phase 1 clinical trial evaluating KH658 gene therapy for wet Age-related Macular Degeneration (wet AMD). The multi-center, open-label, dose-escalation study is being conducted in the United States to assess the safety, tolerability, and efficacy of a single suprachoroidal space administration of KH658 in patients previously treated for wet AMD.
KH658 represents a novel approach to treating wet AMD, a condition affecting approximately 1.5 million Americans. The therapy utilizes a recombinant adeno-associated virus vector that encodes a human VEGF receptor fusion protein, designed to provide continuous anti-VEGF therapy following a single administration.
"Dosing our first patient in the VAN-2401 Phase 1 trial is an important milestone in the advancement of KH658 by exploring the potential of single suprachoroidal space administration of gene therapy as treatment for wet AMD," said Avner Ingerman, M.D., Chief Medical Officer of Vanotech. "KH658 is designed to deliver anti-VEGF continuously to the retina, with the potential to provide sustained levels that can control the disease."
Mechanism of Action and Preclinical Results
In preclinical studies using wet AMD disease models, suprachoroidal administration of KH658 demonstrated retention of the transgene product in the retina for extended periods and prevented disease progression. These findings suggest KH658 could potentially offer a single-administration treatment for wet AMD patients, addressing a significant unmet need in the current treatment paradigm.
The suprachoroidal space administration route represents an important technical advancement in ocular gene therapy delivery. This approach may allow for more targeted delivery to affected tissues while minimizing exposure to other ocular structures.
Trial Design and Patient Population
The VAN-2401 Phase 1 trial (NCT06825858) is expected to include approximately nine subjects with previously treated wet AMD who have demonstrated responsiveness to anti-VEGF therapy. The open-label, dose-escalation design will primarily evaluate safety and tolerability, while also gathering preliminary efficacy data.
Mark Barakat, M.D., a principal investigator in the trial and Director of Research at Retina Macula Institute of Arizona in Scottsdale, expressed enthusiasm about the study: "I am excited to participate as a principal investigator in this important study. Dosing the first patient is an important milestone in the development of the single-administration gene therapy approach, which may hold promise to our patients in need of frequent treatment for their retinal diseases."
Wet AMD: Disease Burden and Current Treatment Landscape
Wet AMD represents the more severe form of age-related macular degeneration, characterized by abnormal blood vessel formation in and under the retina. These vessels leak fluid, disrupting normal retinal architecture and function, ultimately leading to vision loss. If left untreated, wet AMD can cause irreversible blindness.
The current standard of care for wet AMD involves anti-VEGF therapies administered through intravitreal injections. While effective at reducing leakage and fluid accumulation, these treatments typically require frequent injections—often every 4-12 weeks—to maintain efficacy and control disease progression. This treatment burden represents a significant challenge for patients, caregivers, and healthcare systems.
Potential Clinical Impact
If successful, KH658 could transform the treatment paradigm for wet AMD by potentially reducing or eliminating the need for frequent anti-VEGF injections. A single-administration therapy would significantly reduce treatment burden for patients, many of whom are elderly and may face challenges with regular clinic visits.
"The continuous delivery of anti-VEGF therapy through gene expression could potentially provide more consistent disease control than the peaks and troughs associated with periodic injections," explained Dr. Ingerman. "This approach aims to address both efficacy and quality of life considerations for patients with wet AMD."
Company Collaboration
This clinical trial represents a collaboration between Chengdu Origen, a clinical-stage gene therapy company focused on developing treatments for unmet medical needs, and Vanotech, which is serving as the sponsor-representative responsible for the clinical development program of KH658 in the United States.
Vanotech is simultaneously conducting another Phase 1 trial (VAN-2201, NCT05657301) evaluating KH631, another gene therapy candidate for wet AMD, highlighting the company's commitment to developing innovative treatments for retinal diseases.
As the VAN-2401 trial progresses, the companies will evaluate safety data from the initial cohorts before proceeding to higher dose levels. Complete results from this Phase 1 study will inform the design of potential future clinical trials to further evaluate the efficacy and safety of KH658 in larger patient populations.
