4D-150 maintained vision and reduced anti-VEGF injection burden by up to 87% over two years in the PRISM Phase 2b trial for wet AMD, with favorable long-term safety.
Written By: Kirti Kumbhar, M. Pharm (QA)
Reviewed By: Pharmacally Editorial Team
A single intravitreal dose of 4D-150 maintained visual outcomes and retinal anatomy while substantially reducing the need for supplemental anti-VEGF injections over two years in patients with wet age-related macular degeneration (AMD). The latest Phase 2b findings also showed favorable long-term safety profile with no new cases of treatment-related intraocular inflammation beyond the first 28 weeks after dosing.
4D Molecular Therapeutics (4DMT) has reported positive two-year results from the PRISM Phase 2b clinical trial (NCT05197270) evaluating 4D-150, an investigational intravitreal gene therapy for wet AMD. The data, presented at the 44th Annual Scientific Meeting of the American Society of Retina Specialists (ASRS), support the potential of a single administration to provide durable disease control while reducing the long-term treatment burden associated with frequent anti-VEGF injections.
A Gene Therapy for Long-Term Anti-VEGF Delivery
4D-150 is an investigational adeno-associated virus (AAV)-based gene therapy that delivers sustained retinal expression of aflibercept together with an anti-VEGF-C biologic following a single intravitreal injection. The therapy uses 4DMT’s engineered R100 AAV vector, developed through the company’s Therapeutic Vector Evolution platform.
Wet AMD is characterized by abnormal blood vessel growth beneath the retina driven largely by vascular endothelial growth factor (VEGF). Current standard treatment requires repeated intravitreal anti-VEGF injections, often every four to eight weeks, creating a significant burden for patients and retina specialists while affecting long-term treatment adherence.
PRISM Phase 2b Demonstrated Durable Clinical Benefit
The Phase 2b study enrolled 45 patients across two dose levels, including 30 patients who received the selected Phase 3 dose of 3E10 vector genomes (vg)/eye and 15 patients treated with a lower dose. A subgroup of 15 recently diagnosed patients receiving the Phase 3 dose closely reflects the population enrolled in the ongoing 4FRONT Phase 3 trials.
After two years of follow-up, patients maintained best-corrected visual acuity (BCVA) and stable central subfield thickness (CST), indicating sustained functional and anatomical disease control.
The treatment also produced a substantial and durable reduction in supplemental anti-VEGF injections.
In the overall study population, patients required an average of 2.7 supplemental injections over two years, representing a 78% reduction compared with the projected treatment burden expected under the labelled aflibercept 2 mg every 8 weeks regimen. The study was not a head-to-head randomized comparison.
Among recently diagnosed patients, the benefit was even greater, with an average of 1.6 supplemental injections, corresponding to an 87% reduction in treatment burden. Investigators also reported that the higher Phase 3 dose maintained superior efficacy throughout the two-year follow-up.
Safety Profile Remained Stable
While the Phase 2b efficacy analysis included 45 patients, the safety assessment pooled 71 patients treated at the selected Phase 3 dose across the Phase 1/2a and Phase 2b studies, providing a broader evaluation of long-term tolerability.
Only two patients (2.8%) experienced treatment-related mild (1+) intraocular inflammation during approximately the first 28 weeks after dosing. These events were transient and limited to a single observation of mild vitreous cells.
Importantly, no new treatment-related inflammation occurred after the first 28 weeks despite follow-up ranging from two to more than four years. Investigators also reported no treatment-related hypotony, endophthalmitis, retinal vasculitis, or choroidal effusions.
Experts Highlight Long-Term Treatment Potential
David Kirn, M.D., Co-founder, President and Chief Executive Officer of 4DMT, said the two-year results reinforce confidence that 4D-150 could provide durable vision preservation while substantially reducing treatment burden for patients with wet AMD.
Presenting investigator Carl Awh, M.D., FASRS, of Tennessee Retina, noted that maintaining frequent injection schedules remains one of the greatest challenges in retinal care. He said the sustained efficacy observed with a single intravitreal administration could improve long-term disease management and help preserve vision by reducing dependence on repeated injections.
Path Forward
The durable efficacy and favorable safety profile observed in PRISM reinforce the potential of 4D-150 as a one-time intravitreal gene therapy for wet AMD. With the ongoing 4FRONT Phase 3 program evaluating the selected 3E10 vg/eye dose, 4DMT aims to establish a pivotal dataset to support regulatory review. If successful, 4D-150 could transform retinal care by reducing the need for frequent injections while preserving vision long term.
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About the Writer
Kirti Kumbhar (LinkedIn) is an M.Pharm graduate with experience in Quality Assurance at Lupin Limited and a strong interest in clinical research, regulatory affairs, and Trial Master File (TMF) management. She has developed knowledge of regulatory documentation, quality systems, compliance, and healthcare research through her professional experience. Passionate about clinical development and continuous learning, Kirti is committed to supporting high-quality healthcare documentation, regulatory excellence, and research-driven healthcare advancements.