4DMT’S Gene Therapy for AMD Clears Phase II, Heads to Late-Stage Studies

 

4D Molecular Therapeutics reported its experimental gene therapy demonstrated a nearly 90% reduction in the need for annualized standard-of-care injections in patients with wet age-related macular degeneration.

4D Molecular Therapeutics announced on Wednesday that its investigational gene therapy 4D-150 demonstrated durable clinical activity in the Phase I/II PRISM study of patients with wet age-related macular degeneration.

In a 30-patient cohort, 4D-150 cut the need for standard-of-care injections by 89% through 52 weeks of follow-up, and 70% of these patients were injection-free, according to 4DMT’s announcement. In another cohort of 27 patients with severe disease, the need for standard-of-care treatment dropped by 83% and 44% were injection-free.

The gene therapy also resulted in sustained benefits in terms of central subfield thickness and mean best-corrected visual acuity.

In terms of safety, PRISM found 4D-150 to be well-tolerated. The frequency for of intraocular inflammation (IOI) was consistent with approved anti-VEGF therapies, which are currently widely used to treat age-related macular degeneration (AMD). Overall, 4DMT documented two IOI episodes in all 71 wet AMD patients enrolled, yielding an incidence rate of 2.8%.

There were no cases of retinal artery occlusions, hypotony, vasculitis, choroidal effusions and endophthalmitis related to the gene therapy.

4DMT CEO David Kirn in a statement called 4D-150 a “potentially paradigm shifting product candidate,” noting that PRISM’s findings highlight “clear reduction in overall treatment burden and potential multiyear clinical benefit in previously treated patients.” The California-based biotech will continue to invest in 4D-150’s development, Kirn said, and push it into late-stage studies.

Alongside the PRISM readout on Wednesday, 4DMT detailed the design of its Phase III 4FRONT development program for 4D-150, which is set to include two double-masked, randomized non-inferiority trials, compared with on-label treatment with Bayer and Regeneron’s Eylea (aflibercept). The gene therapy will be given at a single 3E10 vg/eye dose.

The first study under this program, dubbed 4FRONT-1, has a target enrollment of 500 patients and is set to start in the first quarter of 2025, Kirn said.

The Phase III program design is in alignment with feedback from the FDA under its Regenerative Medicine Advanced Therapy Designation, according to 4DMT.

4D-150 is an investigational gene therapy that uses an intravitreal vector to deliver a transgene that encodes for aflibercept—the active ingredient of Eylea—and an RNAi molecule that blocks the VEGF-C protein. This mechanism of action allows 4D-150 to suppress four different VEGF proteins in the eye, disrupting the key disease pathway in wet AMD.

With 4D-150, 4DMT is seeking to offer a one-time alternative to Eylea, which is injected into the eye every eight weeks, following an initiation regimen. Eylea has become a top-selling treatment in the ophthalmology space. In 2023, the product brought in $5.9 billion in sales worldwide.

https://www.biospace.com/drug-development/4dmts-gene-therapy-for-amd-clears-phase-ii-heads-to-late-stage-studies