Raj K. Maturi, MD: 4D-150 for nAMD in PRISM Population Extension Cohort

Interim findings from the Phase 2 PRISM population extension cohort demonstrated the efficacy and tolerability of 4D-150 gene therapy for treating neovascular (wet) age-related macular degeneration (nAMD).

These data, presented at the American Society of Retina Specialists (ASRS) 42nd Annual Meeting, showed that 4D-150 reduced the mean annualized anti-vascular endothelial growth factor (VEGF) injection rate by up to 91% and remained well-tolerated in eyes with nAMD.

“The study is continuing. If they need additional treatment, we obviously give it to them,” presenting investigator Raj K. Maturi, MD, Midwest Eye Institute & Retina Partners Midwest told HCPLive. “They’re very straightforward criteria for anti-VEGF supplementation, which includes vision and OCT thickness and then we watch those patients.”

4D-150 is an investigational intravitreal genetic medicine comprised of a retinotopic AAV vector and a dual-transgene cassette encoding aflibercept and miRNA sequence targeting VEGF-C. Interim findings from PRISM’s randomized dose expansion study found that 4D-150 was safe and achieved durable clinical activity versus aflibercept in adults with nAMD and severe disease activity.

PRISM’s Phase 2 population extension cohort focused on adults with nAMD who required 1–6 anti-VEGF injections in the previous 12 months, had fluid on optical coherence tomography (OCT), and a best-corrected visual acuity (BCVA) of 34–83 letters. Endpoints for the analysis included adverse events, supplemental anti-VEGF injections, and change from baseline in BCVA and central subfield thickness (CST).

Patients received intravitreal aflibercept 2 mg on Days –7 and 28 of PRISM. On Day 1, a single intravitreal injection of 4D-150 3/1010 vg per eye was administered to 30 patients, while 15 received 1 x 1010 vg/eye.

By May 2024, 25 and 15 participants in each respective group had completed 24 weeks of follow-up, while the rest had completed 20 weeks follow-up. Interim safety analysis showed no 4D-150-related serious adverse events, vasculitis, endophthalmitis, or hypotony. Viritis was reported in one participant in each dose group.

Meanwhile, the mean number of anti-VEGF injections was reduced by 89% and 91% in the 3x1010 and 1x1010 vg/eye cohorts, respectively. Importantly, 77% and 60% of the respective cohorts remained injection-free and 96% of all participants received ≤1 supplemental injection.

Adjusted mean changes in BCVA at Weeks 20 and 24 were +4.5 ETDRS letters in the 3x1010 vg/eye cohort and –2.5 letters in the 1x1010 vg/eye cohort. Central subfield thickness (CST) remained stable, with an average adjusted change of –4.2m in the 3/x1010 vg/eye cohort and +7.2 m in the 1x1010 vg/eye cohort.

“At this point, given how good the data looks to date, I suspect the company will move forward into phase 3 and have publicly stated that they will use this current high dose [3×1010 vg/eye] in their Phase 3 study,” Maturi told HCPLive.

Disclosures: Relevant disclosures for Raj K. Maturi, MD include Allergan, Genentech, Unity Biotechnology, and others.

Reference

_{Maturi RK. Phase 2 Population Extension Cohort in the PRISM Trial Evaluating 4D-150 in Adults With Neovascular Age-related Macular Degeneration. Paper presented at the American Society of Retina Specialists (ASRS) 42nd Annual Meeting. Stockholm, Sweden. July 17-20, 2024.}