4DMT's Gene Therapy Shows Promise in Diabetic Macular Edema Treatment

4D Molecular Therapeutics (4DMT) has reported encouraging 60-week data from its phase 2 trial of 4D-150, a gene therapy designed to treat diabetic macular edema (DME). The results, presented at the Annual American Society of Retina Specialists Scientific Meeting, demonstrate sustained efficacy and a significant reduction in the need for supplemental injections, potentially offering a breakthrough in DME management.

Efficacy and Durability

The phase 2 trial evaluated single doses of 4D-150, which encodes aflibercept and a sequence that inhibits expression of VEGF-C. Among the nine patients who received the phase 3 dose, researchers observed a gain in best corrected visual acuity of 9.7 letters at 60 weeks, compared to 8.4 letters at the 32-week mark. This improvement suggests a durable effect of the treatment over time.

Reduced Injection Burden

One of the most striking findings was the substantial decrease in the need for supplemental injections. Patients receiving the phase 3 dose experienced a 78% reduction in supplemental injections compared to projected on-label use of aflibercept 2 mg. This reduction increased from 86% at 32 weeks, indicating sustained effectiveness. Notably, four out of nine patients on the phase 3 dose remained injection-free throughout the study period.

Safety Profile

4DMT reported that 4D-150 continues to demonstrate a favorable safety profile. No cases of intraocular inflammation were observed at any timepoint, and patients did not require modifications to their topical corticosteroid regimen. The study also found no instances of hypotony, endophthalmitis, vasculitis, choroidal effusions, or retinal artery occlusion. Mean intraocular pressure remained within normal limits, further supporting the therapy's safety.

Regulatory and Market Implications

The positive results have had a significant impact on 4DMT's market position, with the company's stock climbing more than 40% in premarket trading following the data release. The biotech also shared a regulatory update, revealing that both the European Medicines Agency and the FDA have agreed that a single phase 3 trial could support approval for 4D-150 in DME. This development, coupled with planned studies in wet age-related macular degeneration, positions 4DMT favorably in the competitive landscape of ophthalmic gene therapies.