At the 2024 meeting of the American Society of Retina Specialists in Stockholm, Sweden, Raj Maturi, MD, presented late-breaking data on the dose-expansion cohort of the PRISM trial of 4D-150 (4DMT). The PRISM study is a randomized, controlled phase 2 clinical trial evaluating the gene therapy 4D-150 in previously treated wet AMD patients with severe disease activity (≥325 µm central subfield thickness [CST] measured by optical coherence tomography [OCT] and presence of subretinal or intraretinal fluid) and a high treatment burden (≥6 anti-VEGF injections in the prior 12 months). Enrolled patients were randomized 2:2:1 to receive a single high (3E10 vg/eye) or low (1E10 vg/eye) intravitreal dose of 4D-150 or intravitreal aflibercept 2 mg every 8 weeks (control).
Dr. Maturi presented 6 month data on a group of 45 patients receiving 1 injection of gene therapy at the high or low doses of 4D-150. There was 1 case in each dose group of mild intraocular inflammation. In the higher dose group, there were 0 cases with anterior cells and 1 case with vitreous cells that remained stable over 24 weeks. In the lower dose group, 1 case had 2-3+ vitreous cells at week 24 and topical treatment was used. No additional topical treatment was used in the higher dose group. Data at 6 months also showed 77% of patients in the higher dose group were injection free, and 93% had 1 or fewer injections with improved visual acuity and stable OCT.
“4D-150 was safe and well tolerated through 24 weeks in individuals with wet AMD,” Dr. Maturi told Retinal Physician, noting that there were no cases of hypotony, endophthalmitis, retinal vasculitis, choroidal effusions, or retinal artery occlusions. “These subjects showed a durable improvement of vision, 77% of subjects were supplemental injection free, and 93% had 1 or fewer supplemental injections.”
“We as retina specialists keep looking for drugs that can improve visual acuity in patients with a minimal number of injections or interventions,” Dr. Maturi added. “Gene therapy, especially intravitreal gene therapy done in the office, can potentially be an excellent option in the near future.”
4D-150 is an intravitreal vector, R100, with a transgene cassette that expresses both aflibercept and a VEGF-C inhibitory RNAi. Its dual-transgene payload inhibits VEGF A, B, C, and PlGF. R100 was invented at 4DMT and was developed using principles of directed evolution, a Nobel Prize–winning technology. 4D-150 is designed for single, low-dose intravitreal delivery for transgene expression from the retina without significant inflammation.
