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Analyses of 24-month data from the two pivotal phase III trials investigating a proprietary fluocinolone acetonide-releasing intravitreal insert for the treatment of diabetic macular edema generated positive results that are the basis for filing a new drug application with the FDA.
The Fluocinolone Acetonide in Diabetic Macular Edema (FAME) studies randomly assigned 956 patients 2:2:1 to receive a high-dose FA insert (~0.45 µg/day), a low-dose FA insert (~0.23 µg/day), or sham, said Dr. Campochiaro, FAME investigator and Eccles professor of ophthalmology and neuroscience, Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore.
Results presented were based on all subjects who completed 24 months of follow-up in the two-phase III clinical studies. More than three-fourths of the patients who received the FA insert had received only a single insert.
In the first public presentation of the top-line results for the primary efficacy time point, Dr. Campochiaro reported that for the Full Analysis Set-representing all patients assigned to treatment with last observation carried forward for missing data only, and in both studies separately-significantly higher proportions of patients in both the low-dose and high-dose FA insert groups compared with the sham-treated controls achieved the primary efficacy endpoint (ETDRS BCVA improvement ≥15 letters from baseline at month 24). There was no evidence of a dose-response relationship for efficacy.
Results from a combined dataset showed that about 29% of patients who received the FA insert achieved a 15-letter or greater improvement from baseline BCVA compared with 16.5% of controls.
Efficacy by the numbers
Numerically, efficacy was greater in both FA insert dose groups at month 24 compared with month 18, and analyses of secondary efficacy endpoints-including reduction in retinal thickness, other vision outcomes, and incidence of retinal laser treatment-also showed statistically significant superiority of the FA insert compared with control. Analyses based on a variety of other populations also supported the robustness of the findings in the Full Data Set analysis.
The incidence of corticosteroid-related adverse events was higher among patients in the high-dose versus low-dose FA insert group. An IOP increase of 30 mm Hg or more at any time point was recorded for 21.6% of patients with the low-dose insert and 16.3% of those with the high-dose inserts; rates of trabeculectomy were 5.1% in the high-dose group and only 2.1% in the low-dose group.
Extended release delivery
"The results are important, because they demonstrate that it is possible to provide controlled delivery of an agent to the retina for more than a year after a single injection in the clinic," Dr. Campochiaro said.
"They also demonstrate that the way one delivers steroids to the eye is critical," he added. "Steroid delivery at a very low dose over a long period of time provides benefits to patients with macular edema without the high rate of glaucoma seen with bolus injections or sustained delivery of higher doses."
"We are extremely excited about the benefit-to-risk profile of these results," Ken Green, PhD, chief scientific officer, Alimera Sciences, told Optometry Times. "The data validate the paradigm shift that [the FA insert] represents for the use of corticosteroids in the treatment of DME. We look forward to filing an NDA to register the low-dose FA insert for the treatment of DME.
"Given the significant benefit demonstrated in the pivotal trials," he continued, "which for the first time assessed primary efficacy of a drug for treating retinal disease based on an endpoint of improvement in vision, combined with its favorable safety profile, especially with respect to elevated IOP, we are very enthusiastic about the potential for [the FA insert] to be the first drug approved for the treatment of DME."
Alimera Sciences is on track for filing its NDA this month.
The FA insert is delivered into the vitreous through a self-sealing incision using a 25-gauge injector system. The low-dose insert is expected to deliver medication for up to 3 years.