ANI Pharmaceuticals announced results from the NEW DAY clinical trial evaluating ILUVIEN (fluocinolone acetonide intravitreal implant) for diabetic macular edema (DME) treatment, with mixed outcomes that failed to meet the primary endpoint but showed promise in secondary analyses.
The prospective, multicenter, randomized trial enrolled 306 eyes of treatment-naïve or almost naïve DME patients across approximately 42 U.S. sites. Results were presented by Michael A. Singer, M.D., Clinical Professor of Ophthalmology at University of Texas Health Science Center, at the American Society of Retina Specialists Annual Scientific Meeting.
Primary Endpoint Results
The trial's primary endpoint—mean total number of supplemental aflibercept injections needed over 18 months—was not met. Patients receiving ILUVIEN (n=154) required a mean of 2.4 supplemental aflibercept injections compared to 2.5 in the aflibercept arm (n=152), a difference that was not statistically significant (p=0.756).
However, the secondary endpoint of time to first supplemental injection showed significant benefit for ILUVIEN. The mean time from last treatment injection to first supplemental aflibercept injection was 185.4 days in the ILUVIEN arm compared to 132.8 days in the aflibercept arm (p<0.001).
Post-Hoc Analysis Shows Promise
A post-hoc analysis of patients without major protocol deviations revealed more encouraging results. In this per-protocol population, ILUVIEN patients (n=128) required significantly fewer supplemental aflibercept injections than the aflibercept arm (n=134)—1.8 versus 2.5 injections respectively (p=0.029).
This translated to a substantial difference in total injection burden: ILUVIEN patients received one initial ILUVIEN injection plus a mean of 1.8 supplemental injections (total 2.8), while aflibercept patients received five initial aflibercept injections plus 2.5 supplemental injections (total 7.5).
Clinical Significance and Expert Commentary
"Research suggests that DME is a multifactorial disease driven not only by increased production of VEGF, but also chronic inflammation," said Dr. Singer. "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."
Dr. Singer emphasized that this potential reduction in treatment burden could be critical for DME patients, as their multifactorial disease necessitates multiple visits to medical specialists.
Visual Acuity and Anatomic Outcomes
Secondary endpoints assessing visual acuity and anatomic changes demonstrated non-inferiority between ILUVIEN and aflibercept arms. The mean change from baseline in best corrected visual acuity (BCVA) score over 18 months was 1.8 letters in the ILUVIEN arm versus 5.5 letters in the aflibercept arm (p=0.080), though this did not meet the prespecified non-inferiority margin of 4 ETDRS letters.
Central subfield thickness reduction was similar between groups, with -118.8 μm in the ILUVIEN arm compared to -113.6 μm in the aflibercept arm (p=0.709).
Safety Profile
ILUVIEN was well tolerated with a safety profile consistent with previous clinical trials. In the intent-to-treat population, 41% of ILUVIEN patients experienced treatment-related adverse events, primarily cataract/subcapsular cataract (n=50) and increased intraocular pressure (n=24), compared to 3% in the aflibercept arm.
Sixteen percent of ILUVIEN patients experienced increased intraocular pressure compared to 3% in the aflibercept arm. Among ILUVIEN patients, 11% experienced IOP increases ≥25 mmHg versus 3% in the aflibercept arm, and 4.5% required laser or incisional IOP-lowering intervention compared to 1.3% in the aflibercept arm.
Study Design and Patient Population
The NEW DAY trial was designed as a prospective, multicenter, masked, randomized, active-controlled study. Eligible patients were ≥18 years old with Type 1 or Type 2 diabetes and center-involving DME confirmed by SD-OCT, with central subfield thickness ≥350 μm and BCVA between 35-80 ETDRS letters.
Patients were randomized to receive either a single ILUVIEN intravitreal implant or five monthly aflibercept injections (2 mg) during a 16-week induction period, followed by supplemental aflibercept injections as needed during a 13-month maintenance period.
Company Perspective
"ILUVIEN is already an established treatment option for diabetic macular edema and the results of the NEW DAY trial further highlight its potential as an important option for patients impacted by this disease," stated Nikhil Lalwani, President and Chief Executive Officer of ANI. "We believe these data have the potential to support earlier usage of ILUVIEN as part of its role in reducing treatment burden in DME."
Disease Background
Diabetic macular edema occurs when blood vessels leak into the macula, causing swelling that can lead to blurry vision and vision loss. Approximately 7% of people with diabetes will develop DME over time, with about 4% developing clinically significant macular edema that causes blurred vision and may result in cumulative long-term damage.
ILUVIEN is currently indicated for DME treatment in patients previously treated with corticosteroids who did not experience clinically significant intraocular pressure increases.
