4D Molecular Therapeutics Announces Positive 60-Week Data from SPECTRA Trial Evaluating 4D-150 in DME

4D Molecular Therapeutics (4DMT) has announced positive results from its ongoing SPECTRA clinical trial evaluating 4D-150, an investigational gene therapy for diabetic macular edema (DME). The findings, including both the 52-week primary endpoint and 60-week follow-up data, were presented at the American Society of Retina Specialists (ASRS) 2025 Annual Meeting.

4D-150 is designed to provide long-term intraocular delivery of anti-VEGF therapy (targeting both aflibercept and VEGF-C) through a single intravitreal injection. The therapy is enabled by 4DMT’s proprietary intravitreal vector R100, developed for sustained gene expression in retinal tissue.

Trial Design and Patient Outcomes

The primary goal of the SPECTRA trial was to assess the safety, tolerability, and optimal dose of 4D-150 in patients with diabetic macular edema (DME). A total of 22 patients were enrolled across three dose levels, including 9 patients who received the phase 3 dose of 3E10 vg/eye, 12 patients who received 1E10 vg/eye, and 1 patient who received 5E9 vg/eye.

Two patients from the 1E10 group were excluded from efficacy analysis due to missing over 50% of scheduled visits.

Results showed excellent safety across all groups, with no intraocular inflammation observed over 60 weeks and no adjustments required in topical corticosteroid regimens.

Visual Acuity and Injection Burden

Patients who received the phase 3 dose of 3E10 vg/eye experienced a gain of +9.7 letters in best corrected visual acuity (BCVA) and a reduction of -174 µm in central subfield thickness (CST), as measured by optical coherence tomography (OCT).

In terms of injection burden, patients at the phase 3 dose required an average of 1.6 supplemental injections, compared to 3.7 in lower dose groups. Notably, 44% of patients at the phase 3 dose remained injection-free, compared to just 9% in the lower dose cohorts.

Expert Insights on Clinical Potential

Dr. David Almeida, MD, MBA, PhD, who presented the findings at ASRS, remarked:

“4D-150 has the potential to fundamentally transform the treatment of DME by reducing treatment burden with a product that has adherence by design, while providing meaningful, lasting vision improvement. This is especially important in DME, which frequently occurs in a working-age population.”

Dr. David Kirn, CEO and co-founder of 4DMT, emphasized:

“The consistency of dose response, safety, and efficacy data we’ve seen with 4D-150 in both DME and wet AMD reinforces our belief that this could become a true backbone therapy for retinal vascular diseases.”

Regulatory Alignment with FDA and EMA

Following alignment with the U.S. Food and Drug Administration (FDA) in early 2025, the European Medicines Agency (EMA) has also agreed that a single phase 3 clinical trial, informed by data from SPECTRA, PRISM, and the upcoming 4FRONT wet AMD program, would be acceptable as the basis for a marketing authorization application (MAA) for 4D-150 in DME.