PRISM Interim Analysis Finds 4D-150 Reduces Burden, Treatment Interval with Anti-VEGF Therapy

Arshad Khanani, MD
Credit: Linkedin

New data from an interim analysis of the phase 2 PRISM trial is offering clinicians the greatest insight yet into the effects of 4DMT’s intravitreal dual-transgene payload inhibitor 4D-150 among a broad neovascular (wet) age-related macular degeneration (AMD) population.

Presented at the American Society of Retina Specialists (ASRS) 42nd Annual Scientific Meeting, 24-week interim data from the trial suggested use of the 3E10 vg/eye dose, which is the planned phase 3 dose, offered robust anti-VEGF treatment reductions in the form of an 89% reduction in mean annualized injection rate and 77% of patients remaining injection free at 24 weeks.¹

“Patients suffering from wet AMD face a substantial treatment burden, requiring frequent intravitreal injections throughout their lives, which significantly impacts quality of life not only for the patients themselves but also for their families and caregivers,” said Arshad M. Khanani, MD, MA, director of Clinical Research at Sierra Eye Associates and Clinical Professor at University of Nevada.² “The PRISM Phase 2 data at 24 weeks across multiple populations, and long-term data collected over 2 and a half years, confirms 4D-150’s potential to significantly reduce the treatment burden and maintain vision through a safe, single intravitreal injection. I look forward to contributing to the Phase 3 trial, and to further advancing this treatment option for individuals with wet AMD.”

A multicenter phase 1/2 trial, PRISM was launched in 2021 and enrolled patients with subretinal or intraretinal fluid on optical coherence tomography, a best corrected visual acuity (BCVA) of 34 to 83 letters, and history of anti-VEGF treatment in the prior 12 months. Per trial protocol, there was no minimum or maximum for central subfield thickness (CST).¹

A total of 45 patients were enrolled at 2 dose level arms of 4D-150, with 30 receiving a dose of 3E10 vg/eye and 15 receiving a dose of 1E10 vg/eye. Investigators noted patient characteristics were generally well-balanced, with the overall cohort having a mean CST of 329 μm and mean number of actual injections in the prior 12 months was 4.4.¹

Results of the safety analyses suggested 4D-150 was safe and well-tolerated, with no 4D-150–related serious adverse events or study eye serious adverse events. Specific outcomes from the safety analysis indicated there was no anterior chamber inflammation and no significant vitreous inflammation among those receiving the 3E10 vg/eye dose, with all 30 patients completing local steroid prophylaxis on schedule without the need to resume.¹

Assessment of efficacy endpoints at the aforementioned data cutoff indicated the 3E10 vg/eye arm experienced a mean improvement in BCVA from baseline of +4.2 Early Treatment Diabetic Retinopathy Study (ETDRS) letters and a +4.7 letter improvement observed for injection-free patients. Investigators pointed out the observed results were independent of the number of prior anti-VEGF injections.¹

In their release announcing the 24-week phase 2 interim results, 4DMT noted ongoing with the FDA regarding phase 3 clinical trial alignment, with initiation expected in Q1 2025 and an update on the final phase 3 clinical trial design expected in September 2024. Additionally, the company highlighted 52-week results from the phase 2 PRISM trial were expected in February 2025.¹

“The initial benefits of the current treatment paradigm of repeated bolus anti-VEGF injections are not maintained long-term in wet AMD patients due to undertreatment and fluctuations in retinal thickness, leading to vision loss over time,” said Robert Kim, MD, chief medical officer of 4DMT.² “The data presented on 4D-150 continue to show its promise as a potentially safe, routine and one-time intravitreal treatment with the long-term objective to preserve vision for millions of wet AMD patients, regardless of their treatment burden or disease severity.”

References:

1. Maturi RK. 4D-150 Initial Interim 24-week Landmark Analysis from PRISM Phase 2 Population Extension Cohort in Broad Wet AMD. Paper presented at the American Society of Retina Specialists (ASRS) 42nd Annual Meeting. Stockholm, Sweden. July 17-20, 2024.
2. 4D Molecular Therapeutics, Inc. 4DMT announces Positive phase 2 prism interim results for Intravitreal 4D-150 in a broad wet amd population affirming favorable safety profile and robust clinical activity. GlobeNewswire News Room. July 17, 2024. Accessed July 17, 2024. https://www.globenewswire.com/en/news-release/2024/07/17/2914359/0/en/4DMT-Announces-Positive-Phase-2-PRISM-Interim-Results-for-Intravitreal-4D-150-in-a-Broad-Wet-AMD-Population-Affirming-Favorable-Safety-Profile-and-Robust-Clinical-Activity.html.