4DMT announces positive 52-week data from phase 2b cohort of PRISM wet AMD study

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4D Molecular Therapeutics announced positive interim 52-week data from its Phase 2b Population Extension cohort of the PRISM clinical trial evaluating 4D-150 in a broad wet age-related macular degeneration (wet AMD) patient population.

4D-150 is a potential backbone therapy designed to provide multi-year sustained delivery of anti-VEGF (aflibercept and anti-VEGF-C) from the retina with a single, safe, intravitreal injection.¹

The data were presented by Dante Pieramici, MD, in an oral presentation at Angiogenesis, Exudation, and Degeneration 2025.

"The promise of 4D-150 for both patients and clinicians lies in its potential to tackle one of the most pressing unmet needs in vascular retinal diseases—providing a long-lasting, effective treatment option that reduces the frequent burden of bolus anti-VEGF injections,” said Pieramici.“4D-150 offers a profound shift in how we manage our patients’ care, potentially freeing them from the ongoing challenges of injection frequency while ensuring they maintain the vision improvement characteristic of current standard of care. The data from the PRISM study gives me great hope that 4D-150 can become the backbone of future retinal treatments for wet AMD, offering both clinical benefit and better quality of life for our patients."

Data from the 2b trial (n=30) in broad wet AMD showed an 83% reduction in supplemental aflibercept injections, representing 0.97 mean supplemental injections per patient over 52-weeks compared to 6.0 injections projected with on-label aflibercept 2 mg Q8W. Furthermore, 70% required 0 or 1 supplemental injection while 57% were supplemental injection-free.¹

Additionally, treatment with 4D-150 improved and maintained best corrected visual acuity (BCVA) of +2.2 letters. Durable central subfield thickness (CST) improvement was also seen with fewer fluctuations, as measured by optical coherence tomography (OCT), of -11 µm; -13 µm in supplemental injection-free patients.

Data from the recently diagnosed subgroup (n=15) showed a 94% reduction in supplemental injections, representing 0.33 mean supplemental injections per patient over 52-weeks vs. 6.0 injections projected with on-label aflibercept 2 mg Q8W. Additionally, 87% required 0 or 1 supplemental injection while 80% were supplemental injection-free.¹

An improved and maintained BCVA of +3.1 letters was seen in the recently diagnosed subgroup, as well as durable CST improvement with fewer fluctuations, as measured by OCT, of -10 µm; -20 µm in supplemental injection-free patients.

According to the company, 4D-150 continues to be well tolerated during up to 3 years of follow-up in all patients treated with 3E10 vg/eye. No 4D-150–related hypotony, endophthalmitis, vasculitis, occlusive/non-occlusive retinal vasculitis, or choroidal effusions have been observed to date.

The company also noted that 4FRONT-1 and 4FRONT-2 are expected to initiate in Q1 and Q3 2025, respectively and 2-year Phase 1/2a and 18-month Phase 2b PRISM data is expected in Q4 2025.¹

Reference:

1. 4DMT Presents Positive 52-Week Results from Phase 2b Cohort of PRISM Wet AMD Study and Long-term Durability Data Supporting 4D-150 4FRONT Global Registration Program. Published February 8, 2025. Accessed February 10, 2025.https://www.globenewswire.com/news-release/2025/02/08/3023106/0/en/4DMT-Presents-Positive-52-Week-Results-from-Phase-2b-Cohort-of-PRISM-Wet-AMD-Study-and-Long-term-Durability-Data-Supporting-4D-150-4FRONT-Global-Registration-Program.html