4DMT’s Gene Therapy Reduces Eylea Injections, Advancing Plans for Phase 3 Trial in Wet AMD

4D Molecular Therapeutics (4DMT) has reported a 90% reduction in treatment burden for patients with wet age-related macular degeneration (wet AMD) through the use of their gene therapy, 4D-150. This treatment utilizes an adeno-associated virus vector to deliver aflibercept (the molecule in Eylea) and RNAi to inhibit VEGF-C. The gene therapy was tested in a phase 2 dose-expansion cohort with 51 wet AMD patients, showing an 89% and 85% decrease in annualized anti-VEGF injection rates with the high and low 4D-150 dose arms, respectively. Two-thirds of patients on the high dose were injection-free at 24 weeks. 4DMT also noted reduced central subfield thickness variability, which predicts legal blindness. Stable visual acuity was observed across treatment arms, with Eylea numerically beating the high-dose 4D-150 treatment at the 24-week analysis.

4DMT is planning a phase 3 trial in the first quarter of 2024 to demonstrate the noninferiority of the high dose of 4D-150 to aflibercept on best-corrected visual acuity (BCVA). The company intends to enroll 225 patients per arm, reaching a broader wet AMD population. Shares of 4DMT rose around 30% following the positive results.

For context, Eylea has been administered worldwide since its launch, with over 64 million Eylea injections given globally as of the information in 2023. 4DMT follows Regenxbio and AbbVie's ABBV-RGX-314 in developing a wet AMD gene therapy, although 4DMT's approach, incorporating VEGF-C inhibition, provides a potential point of differentiation.