Interim results from the PRISM randomized phase 2 dose expansion trial evaluating 4D-150 in high anti-VEGF need individuals with neovascular (wet) age-related macular degeneration

Abstract

Purpose : 4D-150 is an intravitreal (IVT) genetic medicine comprising the retinotropic AAV vector R100 and a dual-transgene cassette containing a codon-optimized sequence encoding aflibercept (AFLB) and an miRNA sequence targeting VEGF-C. In the PRISM Phase 1 dose exploration study, IVT administration of 4D-150 (6×10⁹ – 3×10¹⁰ vg/eye) to adults with high anti-VEGF need neovascular (wet) age-related macular degeneration (nAMD) was well tolerated and resulted in durable clinical activity. Here we report initial results from the PRISM randomized phase 2 dose expansion study.

Methods : PRISM is an ongoing, multicenter, open-label dose exploration and randomized expansion study (NCT05197270). In the phase 2 dose expansion stage, adults (age ≥50 y) with study eye macular neovascularization secondary to AMD and best corrected visual acuity (BCVA) of 34–83 letters were randomly assigned (2:2:1) to receive a single IVT injection of 4D-150 (3×10¹⁰ or 1×10¹⁰ vg/eye) or IVT AFLB 2 mg administered every 8 weeks. Study outcomes include the incidence and severity of adverse events, the annualized number of supplemental anti-VEGF injections, and change from baseline in BCVA and central subfield thickness.

Results : In the randomized dose expansion phase, 51 participants received a single IVT injection of 4D-150 1×10¹⁰ vg/eye (n=21) or 3×10¹⁰ vg/eye (n=20) or bimonthly injections of aflibercept 2 mg (n=10). Demographics and baseline characteristics are summarized in Table 1. As of 1 November 2023, the duration of follow-up ranged from 12 to 36 weeks. Initial safety results demonstrated that 4D-150 was safe and well tolerated. There were no 4D-150–related serious adverse events, no grade 1 or higher intraocular inflammation, and no endophthalmitis, retinal vasculitis, retinal artery occlusion, or hypotony.

Conclusions : Initial safety results from the PRISM phase 2 dose expansion study evaluating 4D-150 in adults with nAMD were consistent with observations from the dose exploration study, with no evidence of clinically significant ocular adverse events during follow-up for 12–36 weeks. 24-week interim safety and efficacy data will be presented.

This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.

 

Table 1. Demographics and baseline characteristics