NEW YORK – 4D Molecular Therapeutics on Wednesday shared details on the design of a planned registrational Phase III trial for 4D-150, its gene therapy candidate for wet age-related macular degeneration.
4DMT is planning for investigators to compare a single dose of 4D-150 to standard care comprising a regimen of Regeneron Pharmaceuticals' Eylea (aflibercept) within the global study, dubbed 4FRONT. The company said investigators will measure patients' best-corrected visual acuity, with a primary endpoint of noninferiority between the two groups.
Emeryville, California-based 4DMT expects to enroll 500 wet AMD patients into the clinical trial. The company reaffirmed plans announced earlier this year to launch the Phase III trial in Q1 2025.
"We have worked closely with global regulatory agencies and our ophthalmology advisory board to maximize the probabilities of clinical, regulatory, and commercial success of the 4FRONT Phase III program," Carlos Quezada-Ruiz, senior VP and therapeutic area head in ophthalmology at 4DMT, said in a statement.
Wet AMD is a retinal disorder caused by abnormal blood vessels stimulated by VEGF, which is typically treated with repeated anti-VEGF injections such as Eylea. 4DMT aims to treat wet AMD with a one-time gene therapy that delivers a dual transgene payload expressing the aflibercept protein and an RNA interference molecule to inhibit VEGF-C, which, together, are designed to block four VEGF proteins.
4D-150 has demonstrated durable clinical activity based on interim follow-up data from the Phase I/II PRISM trial, according to 4DMT.
In patients with severe wet AMD tested within a Phase I/IIa portion of the trial, 83 percent of patients experienced a reduction in annual injections of supplemental anti-VEGF injections, and 44 percent were injection-free through 52 weeks. In a broad population of wet AMD patients tested within a Phase IIb portion of the trial, 89 percent of patients experienced a reduction in annual injections and 70 percent were injection-free after a year.
4DMT said 4D-150 has been well tolerated and has a favorable safety profile.