NEW DAY trial of ILUVIEN for DME does not meet primary end point; post hoc analysis suggests potential benefits

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ANI Pharmaceuticals announced results from its NEW DAY clinical trial of ILUVIEN (fluocinolone acetonide intravitreal implant), 0.19 mg for patients with diabetic macular edema (DME).

ILUVIEN is a corticosteroid indicated for treating DME in patients previously treated with a course of corticosteroids who did not have a clinically significant rise in intraocular pressure (IOP).

NEW DAY is a prospective, multicenter, masked, randomized, active-controlled trial that enrolled 306 eyes of treatment-naive, or almost naive, DME patients at approximately 42 sites around the US. Patients enrolled were older than 18 years with a diagnosis of type 1 or type 2 diabetes with a center-involving DME confirmed by SD-OCT, and CST of ≥ 350 µm and best corrected visual acuity (BCVA) of ≥35 ETDRS letters and ≤80 ETDRS letters in the study eye at the screening visit. The trial's primary end point was the mean total number of supplemental aflibercept injections needed for the treatment of DME in the ILUVIEN arm compared to the aflibercept arm over the 18-month study period in the intent-to-treat (ITT) population.

Patients were randomly assigned to either an ILUVIEN arm (n=154), where they received an ILUVIEN intravitreal implant, or an aflibercept arm (n=152), where they received 5 injections of anti-VEGF therapy (intravitreal aflibercept 2 mg) at 4-week intervals for the first 16 weeks of the trial during an induction period.

At the end of the 16-week induction period, patients in both arms were evaluated every 4 weeks during a 13-month maintenance period and received supplemental aflibercept injections only as needed.

According to the company, treatment with ILUVIEN demonstrated a numerical reduction in the mean number of supplemental aflibercept injections compared with the aflibercept arm. However, it did not reach the threshold for statistical significance (2.4 vs. 2.5; P = .756), and therefore the primary end point was not met. The secondary end point of mean time from last treatment injection to first supplemental aflibercept injection was met with a mean time of 185.4 days in the ILUVIEN arm, compared to 132.8 days in the aflibercept arm (P < .001). Additionally, 33% of patients in the ILUVIEN arm did not require a supplemental injection during the study compared to 30% in the aflibercept arm.

Secondary end points that assessed visual acuity and anatomic changes in the ITT population demonstrated noninferiority between the ILUVIEN arm and the aflibercept arm, and additional secondary end points will be further evaluated by the company.

A post hoc analysis was conducted on a subset of randomly assigned patients without major protocol deviations, which showed that the ILUVIEN arm (n=128) demonstrated a statistically significant difference in the mean number of supplemental aflibercept injections compared to the aflibercept arm (n=134), with 1.8 vs 2.5 injections, respectively (P = .029). Therefore, patients in the post hoc analysis received a total of 2.8 injections in the ILUVIEN arm, whereas the aflibercept arm patients received a total of 7.5 injections.

Michael A. Singer, MD, clinical professor of ophthalmology at the University of Texas Health Science Center and director of clinical research at Medical Center Ophthalmology Associates in Texas, commented on the results in a press release.

“The NEW DAY study provides clinically meaningful data on ILUVIEN’s potential impact on treatment burden, including a statistically significant difference in time to first supplemental injection of aflibercept in the ILUVIEN arm compared to the aflibercept arm. This potential reduction in treatment burden can be critical for our patients with diabetic macular edema, as their disease is multifactorial, necessitating multiple visits to medical specialists.”

Safety data were reported as “consistent with data from prior ILUVIEN clinical trials and real-world use.” In the ITT patient population, 41% of patients in the ILUVIEN arm experienced treatment-related treatment-emergent adverse events, compared with 3% in the aflibercept arm. The company notes that these were mainly associated with cataract/subcapsular cataract (n=50) and an increase in IOP (n=24). Additionally, 16% of patients in the ILUVIEN arm experienced an increase in IOP compared with 3% in the aflibercept arm, whereas 11% of patients experienced an increase in IOP of ≥25 mm Hg compared with 3% in the aflibercept arm.

References:

1. ANI Pharmaceuticals Announces Results from NEW DAY Clinical Trial of ILUVIEN® for Use in Patients with Diabetic Macular Edema (DME). Published July 23, 2025. Accessed July 24, 2025. https://www.globenewswire.com/de/news-release/2025/07/23/3120083/0/en/ANI-Pharmaceuticals-Announces-Results-from-NEW-DAY-Clinical-Trial-of-ILUVIEN-for-Use-in-Patients-with-Diabetic-Macular-Edema-DME.html