July 19, 2026 —
4D Molecular Therapeutics reported two-year data from the PRISM Phase 2b clinical trial evaluating 4D-150, an investigational AAV-based retinal gene therapy, in patients with wet age-related macular degeneration, or wet AMD.
The data were presented by Carl Awh, M.D., FASRS, of Tennessee Retina, at the 44th Annual Scientific Meeting of the American Society of Retina Specialists. The Phase 2b trial enrolled 45 patients across two dose levels of a single intravitreal dose of 4D-150. The 3E10 vg/eye dose has been selected for the ongoing 4FRONT Phase 3 clinical trials.
4D-150 is designed as a one-time intravitreal AAV gene therapy to provide multi-year, and potentially lifelong, sustained delivery of anti-VEGF biologics within the retina. The therapy is being developed for wet AMD and diabetic macular edema.
Across the two-year follow-up period, patients showed consistent maintenance of best corrected visual acuity and control of central subfield thickness, supporting the therapy’s potential for sustained disease control after a single AAV-based administration.
The overall patient cohort achieved a 78% reduction in treatment burden, with an average of 2.7 supplemental injections per patient compared with 12.0 projected injections using on-label aflibercept 2 mg every eight weeks.
A subgroup of recently diagnosed patients, defined as those diagnosed within six months of enrollment, showed an 87% reduction in treatment burden, with an average of 1.6 supplemental injections per patient.
Safety data from the combined Phase 1/2a and Phase 2b studies, covering 71 patients, showed that 2.8% experienced mild intraocular inflammation within the first 28 weeks. No new cases were reported beyond that period.
No cases of hypotony, endophthalmitis, vasculitis, occlusive or non-occlusive retinal vasculitis, or choroidal effusions have been observed across the study population to date.
Wet AMD remains a major cause of vision loss and requires frequent anti-VEGF injections to preserve vision in many patients. 4DMT’s data suggest that 4D-150 may offer a durable AAV-mediated approach that reduces injection burden while maintaining visual and anatomic outcomes.
The ongoing 4FRONT Phase 3 program will be important in determining whether 4D-150 can confirm these findings in a larger pivotal setting and support a potential path toward regulatory review.
