4D Molecular Therapeutics (4DMT) reported positive interim results from part 1 of the SPECTRA trial evaluating 4D-150 for diabetic macular edema (DME). The 3E10 vg/eye dose demonstrated notable efficacy, achieving sustained visual acuity gains (+8.4 letters) and central subfield thickness (CST) reductions (-194 µm) through 32 weeks, the company said in a press release. This dose also reduced injection burden by 86% compared to standard aflibercept regimens, with a mean of 0.6 supplemental injections per patient. 4D-150 was well tolerated, with no intraocular inflammation or serious safety concerns observed, the company said.

According to 4DMT, the SPECTRA trial is investigating intravitreal 4D-150, an intravitreal gene therapy using an evolved intravitreal vector, R100, and a transgene cassette that expresses both an aflibercept-like protein and VEGF-C inhibitor RNAi, inhibiting VEGF A, B, C, and PIGF. The FDA has aligned with 4DMT’s proposed Phase 3 trial design, enabling the company to bypass part 2 of SPECTRA. The Phase 3 trial, according to the company, will assess BCVA noninferiority vs on-label aflibercept with less stringent supplemental injection criteria, involving 300 to 400 patients.

4D-150’s design aims to deliver multiyear sustained VEGF inhibition with a single intravitreal injection, to address the significant unmet need in DME management by improving adherence and vision outcomes. Detailed findings will be shared in a corporate webcast on Feb. 10, 2025, the company said.