4D Molecular Therapeutics (Nasdaq: FDMT), based in Emeryville, California, announced two-year data from the PRISM Phase IIb trial evaluating 4D-150 in wet age-related macular degeneration, presented at the American Society of Retina Specialists meeting and detailed in a press release. The results extend follow-up on 4DMT's lead candidate beyond one year, providing longer-term evidence for a gene therapy designed to replace chronic anti-VEGF injections with a single administration.
4D-150 is an intravitreal AAV vector encoding both an aflibercept-like anti-VEGF-A/B fusion protein and a microRNA targeting VEGF-C, designed to continuously suppress the VEGF signaling that drives choroidal neovascularization in wet AMD. This dual-pathway suppression differs mechanistically from standard anti-VEGF biologics, which require repeat dosing because they clear from the eye within weeks.
In the trial's overall cohort (n=45, two doses tested), patients maintained visual acuity and anatomic control through two years, with a 78% reduction in treatment burden — 2.7 mean supplemental injections annually versus a projected 12 with Regeneron's Eylea (aflibercept) dosed every eight weeks. A recently diagnosed subgroup, considered most comparable to the population enrolled in the ongoing 4FRONT Phase III trials, showed an 87% burden reduction. Dose response favored the 3E10 vg/eye dose selected for Phase III. Pooled safety data across 71 patients treated at the Phase III dose showed no new intraocular inflammation cases after the first 28 weeks, with mild inflammation in 2.8% of patients earlier in follow-up; no hypotony, endophthalmitis, or retinal vasculitis was reported.