Fluocinolone Acetonide Implant as a Baseline Therapy for Diabetic Macular Edema: Results from the Randomized Phase 4 NEW DAY Study.

Abstract

The NEW DAY (NCT04469595) study assessed the efficacy and safety of the fluocinolone acetonide (FAc; 0.19 mg) intravitreal implant as baseline therapy in diabetic macular edema (DME). Prospective, randomized, single-masked, active-controlled, multicenter, 18-month, phase 4 study. Adults with type 1 or 2 diabetes and center-involving DME confirmed by central subfield thickness (CST). Treatment regimens were FAc implant followed by rescue supplemental injections of aflibercept if needed (2 mg/0.05 mL) for 17 months versus aflibercept loading dose (2 mg every 4 weeks, for 5 consecutive doses) followed by rescue supplemental injections of aflibercept if needed (2 mg/0.05 mL) for 13 months. The primary endpoint was mean rescue supplemental injections of aflibercept needed during the study by treatment group. Additional outcomes included time to first rescue supplemental injection, best-corrected visual acuity (BCVA), CST, rates of cataract procedures, and increases in intraocular pressure (IOP). 517 participants were screened, 306 randomized. Mean (SD) rescue supplemental injections were 2.4 (3.2) with FAc and 2.5 (3.1) with aflibercept (P=0.76; primary endpoint). Counting both protocol-mandated and rescue supplemental injections, the FAc group received fewer injections compared with the aflibercept group (3.4 [3.2] vs. 7.2 [3.4] injections; nominal P<0.001). Time to first rescue supplemental injection was longer with FAc than aflibercept (mean [SD] 185.4 [97.9] vs. 132.8 [94.0] days; nominal P<0.001). Proportions of participants who did not receive rescue supplemental injections were similar (32.5% vs. 30.3%; nominal P=0.68). Mean change in BCVA was similar between groups (1.8 vs. 5.5 letters; nominal P=0.08) as was the change in CST (mean [SD] -119 [112] vs. -114 [103] μm; nominal P=0.71). In the FAc group, 27.9% received a cataract procedure versus 6.6% in the aflibercept group. Increased IOP occurred in 15.6% and 3.3% of participants in the FAc and aflibercept groups, respectively. Although the primary endpoint of rescue supplemental injection superiority was not met, FAc-treated participants achieved similar visual and anatomic improvements as those receiving aflibercept with fewer than half the number of total injections throughout the study. Safety data results were consistent with previous FAc implant studies.