The director of clinical research at Sierra Eye Associates discussed the latest results from a clinical trial evaluating 4D Molecular Therapeutics’ gene therapy, 4D-150, that were presented at ARVO’s 2023 conference.
“[The] majority of the patients need frequent injections—and that's the biggest unmet need, where the treatment burden is so high for many of these patients that they don't get the adequate number of injections that they need. And that's why in [the] real world, we see visual acuity outcomes that are worse than what we see in clinical trials. So there is really an unmet need for having durable agents and sustained delivery of anti-VEGF. Gene therapy is one modality to address this treatment burden and hopefully stabilize visual acuity and improve long-term outcomes in the real world.”
The current standard of care for patients with wet age-related macular degeneration (AMD) consists of regular treatment with Aflibercept, an antivascular endothelial growth factor (VEGF) injection. While Aflibercept can stabilize the disease and prevent further degeneration of vision, it has a high treatment burden because it typically requires patients to receive injections every 4 to 8 weeks to maintain optimal efficacy. As a result of this, in real-world settings, patients often experience some level of vision degeneration because of not keeping up with these injections regularly.
4D Molecular Therapeutics’ 4D-150, an investigational dual-mechanism gene therapy, is intended to address this unmet need by encoding transgenes for Aflibercept and an interference mRNA meant to block VEGF-C. The company expects that a 1-time treatment with a single injection of 4D-150 has the potential to allow for sustained production of these gene products in patients’ retinas.
Arshad Khanani, MD, the director of clinical research and director of Fellowship at Sierra Eye Associates, gave an oral presentation entitled, “Interim results for the phase 1/2 PRISM trial evaluating 4D-150, a dual-transgene intravitreal genetic medicine in individuals with neovascular (wet) age-related macular degeneration,” at the Association for Research in Vision and Ophthalmology (ARVO) 2023 Annual Meeting, held April 23-27, 2023, in New Orleans, Louisiana. The presentation covered the current data on the therapy to date that suggest that a dose response in favor of the high dose (3x1010 vg/eye), including reduction in supplemental anti-VEGF injections and in mean central subfield thickness (CST). All told, following 4D-150 administration, clinically-meaningful improvement of –92 µm in CST was shown at 36 weeks, as was stable best corrected visual acuity. The phase 2 dose-expansion stage of the PRISM trial (n = 50) is currently more than 50% enrolled, with enrollment expected to complete later this year.
In an interview with CGTLive™, Khanani gave background information about the current standard of care for wet AMD and explained how 4D-150 has the potential reduce treatment burden for patients with this disease. He also gave an overview of the promising safety and efficacy data presented at ARVO. Of note, he pointed out that in the highest dose cohort in the PRISM trial, 4 of 5 patients remained free of anti-VEGF injections at 24 weeks after treatment with 4D-150.