4D Molecular Therapeutics (4DMT) announced positive results from the SPECTRA clinical trial evaluating 4D-150 in patients with diabetic macular edema (DME), and alignment with the European Medicines Agency (EMA) on a registrational pathway for 4D-150 in DME. The data, which included both the 52-week primary endpoint and 60-week analyses, were presented by David Almeida, MD, MBA, PhD, Erie Retina Research, in an oral presentation titled “Interim Results from the SPECTRA Phase 2a Clinical Trial Evaluating Intravitreal 4D-150 in Adults with Diabetic Macular Edema” at the Annual American Society of Retina Specialists (ASRS) Scientific Meeting.

“The positive results from the SPECTRA trial demonstrate the tolerability and consistent, durable clinical activity of 4D-150 in DME, highlighting the potential for the product candidate to become a backbone therapy that can dramatically reduce treatment burden compared to the labeled regimen of standard-of-care aflibercept 2 mg every 8 weeks,” said Dr. Almeida in a press release issued by 4DMT. “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.”

The objectives of the study was to evaluate safety and tolerability, and identify dose level for further evaluation. The study population included enrolled patients with high disease activity as measured by central subfield thickness (CST). According to the study, 22 patients enrolled across 3 dose levels included: 3E10 vg/eye (n=9) (phase 3 dose), and lower doses (1E10 vg/eye, n=12; 5E9 vg/eye, n=1)—2 patients dosed with 1E10 vg/eye missed >50% of study visits and were considered not evaluable for injection burden or other efficacy parameters

In addition, the safety results through 60 Weeks (n=22) were as follows: 4D-150 was well tolerated with no intraocular inflammation at any timepoint—no subjects required modification to the topical corticosteroid regimen, and all patients are currently off corticosteroids. There was no hypotony, endophthalmitis, vasculitis, choroidal effusions or retinal artery occlusions were reported, and mean intraocular pressure was within normal limits. 

The efficacy results through 60 weeks were as follows: Utilized stringent supplemental aflibercept criteria to maximize patient safety while assessing initial clinical activity. 

With the phase 3 dose, there was sustained gain of best corrected visual acuity (BCVA) of +9.7 letters, and sustained improvement in anatomic control, with reduction of CST, as measured by optical coherence tomography (OCT), of -174 µm. 

Regarding supplemental injections, post-aflibercept loading doses (3), patients treated with phase 3 dose required substantially fewer supplemental injections compared to patients receiving lower doses or projected on-label aflibercept 2mg Q8W (expected phase 3 comparator):

• Mean supplemental injections per patient:

  • Phase 3 dose: 1.6

  • Lower doses: 3.7

  • Projected on-label aflibercept 2mg Q8W: 7.0

  • Dose response observed for Phase 3 dose vs lower doses (58% fewer injections)

  • Phase 3 dose demonstrated a reduction of 78% vs. projected on-label aflibercept 2mg Q8W

• 0-1 injections:

  • 5 of 9 overall (phase 3 dose) vs 2 of 11 (lower doses)

• Injection-free:

  • 4 of 9 overall (Phase 3 dose) vs 1 of 11 overall (lower doses)

Following US Food and Drug Administration (FDA) alignment, as communicated in January 2025, EMA is also aligned that a single phase 3 clinical trial, based on data generated to date for 4D-150 in both the SPECTRA and PRISM clinical trials combined with data from the 2 planned phase 3 clinical trials in the 4FRONT wet age-related macular degeneration (wet AMD) program, would be acceptable as the basis for a marketing authorization application (MAA) submission for 4D-150 in DME.