Arshad Khanani, MD, on Comparing Wet AMD Gene Therapy 4D-150 to Aflibercept in a Randomized Clinical Trial


The assistant professor in the department of pediatrics at the University of Florida College of Medicine discussed also discussed the latest results announced from the phase 2 portion of the PRISM study.

“I'm thrilled to see these results in terms of efficacy and safety. Because of these positive results, the program is moving forward into the phase 3 pivotal stage.”

Currently, the standard of care (SOC) treatment option for patients with wet age-related macular degeneration (AMD) involves repeated injections of an antivascular endothelial growth factor (VEGF) drug such as aflibercept. For some patients, these injections are needed about every 2 months in order to maintain stability of vision, but because of the high burden of receiving this treatment, many patients do not actually receive injections with ideal frequency in the real-world setting. As such, many patients with wet AMD tend to experience additional loss of vision over time. 4D Molecular Therapeutics (4DMT) is currently developing 4D-150, an investigational dual-mechanism gene therapy, with the intention of overcoming this limitation of the SOC treatment approach. 4D-150 is intended to provide patients’ cells with the ability to consistently produce both aflibercept and an interference RNA for VEGF-C after a single, 1-time injection. The gene therapy is currently being evaluated in the phase 1/2 PRISM clinical trial (NCT05197270). Notably, positive interim results from the randomized-control phase 2 portion of PRISM, which included patients with particularly high-need for antiVEGF injections,were recently announced by 4DMT in February of this year.

Shortly after the announcement, CGTLive® sat down with lead principal investigator Arshad Khanani, MD, the director of clinical research and director of Fellowship at Sierra Eye Associates, to learn more about the latest findings. Khanani provided some background information about 4D-150 and the PRISM study, and then went over the new data in detail. He emphasized that patients treated with 4D-150 showed much less fluctuation in central subfield thickness (CST) compared to patients treated with aflibercept in the control arm. Khanani also went over the continued promising safety outcomes seen with the gene therapy in PRISM, noting that there were no serious adverse events related to 4D-150 observed.

1. 4DMT presents positive interim data from randomized phase 2 PRISM clinical trial of intravitreal 4D-150 demonstrating favorable tolerability & clinical activity in wet AMD. News release. 4D Molecular Therapeutics. February 3 ,2024. Accessed March 11, 2024.
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