Phase 4 Study of Iluvien for DME Shows Statistically Significant Improvements in BCVA, CST, and Treatment Burden at 36 Months

Alimera Sciences announced that the 3-year results of the PALADIN study have been published in the peer-reviewed journal Ophthalmology.

These study results show that patients with diabetic macular edema (DME) who received a single dose of the sustained release implant Iluvien (fluocinolone acetonide intravitreal implant) 0.19 mg demonstrated statistically significant improvements in best corrected visual acuity, central subfield thickness, and treatment burden at 36 months. Treatment frequency for patients in the PALADIN study was reduced by 70.5% from a median of 3.4 treatments per year in the 36 months preceding the injection of Iluvien to a median of 1.0 treatments per year in the 36 months following the Iluvien injection. Further, 2.97% of eyes required IOP lowering surgery, only half of which were due to steroid induced ocular hypertension following the administration of Iluvien in accordance with the U.S. label. This compares favorably to the 4.8% in the pivotal FAME Studies. For full publication, click Here.

A post hoc analysis of 36-month data from PALADIN found that patients with ≤6 treatments for DME before Iluvien administration experienced significantly higher visual acuity gains from baseline compared with patients who had >6 treatments before receiving Iluvien (5.70 letters, P=.0048 vs 1.78 letters, P = .8337). These findings suggest that use of Iluvien earlier in a treatment algorithm for DME could lead to more desirable visual acuity outcomes.

“We are very pleased to see confirmation from the PALADIN study that the side effect risk of intraocular pressure can be effectively mitigated when Iluvien is used in accordance with our U.S. FDA label,” Rick Eiswirth, Alimera’s President and CEO, said in a company news release. “Additionally, we are excited that the PALADIN Study provides another data set demonstrating Iluvien's ability to improve visual acuity with fewer treatment interventions and further supports the hypothesis of our NEW DAY Study.”

The PALADIN study was a phase 4, open-label, prospective, observational study conducted over 36 months at 41 sites across the United States. The study was designed and developed to confirm the benefit of using a prior course of corticosteroid as indicated in the Iluvien US label, to mitigate the risk uncontrolled IOP elevation. Researchers enrolled 202 eyes in 159 patients with DME who had previously received corticosteroid treatment without a clinically significant rise in IOP. All eyes were treated with Iluvien and patients were followed for up to 36 months.

“The 3-year results of the PALADIN study demonstrate Iluvien's ability to safely and effectively improve visual acuity and retinal anatomy while also reducing the recurrence of edema as evidenced by the decreased treatment burden in patients with DME,” Michael Singer, MD, Clinical Professor of Ophthalmology, University of Texas Health Science Center, San Antonio, and Director of Clinical Research Medical Center Ophthalmology, San Antonio, Texas, said in the news release. “This is especially important for the diabetic population. Many diabetics are actively working and would otherwise be subject to a high treatment burden of injections that are currently required with anti-vegf therapy alone These findings further support that earlier use of Iluvien in a treatment algorithm for DME could lead to more desirable anatomical and functional outcomes.”

Primary outcomes included changes in IOP and interventions to manage IOP elevations; secondary outcomes examined visual, anatomic, and treatment burden–related outcomes. Among the findings at 36 months:

• Mean best corrected visual acuity increased by 3.61 letters (P=.0222) from baseline.
• Mean central subfield thickness decreased by 60.69 µm (P<.0001) from baseline.
• Patients received median 1.0 treatment per year after receiving Iluvien. In the 36-month period immediately preceding Iluvien administration, patients received median 3.4 treatments per year. Thus, Iluvien treatment resulted in a 70.5% reduction in treatment burden.
• Surgery to address elevated IOP occurred in 2.97% of eyes; only 1.49% of patients received surgery due to steroid related IOP elevation, with the remaining cases of IOP elevation chiefly attributed to neovascular glaucoma.
• IOP response ≤25 mm Hg after the steroid challenge predicted a similar outcome after Iluvien treatment at the final visit in 96.9% of eyes.
• Mean IOP remained stable throughout the study, and IOP increases of >30 mm Hg occurred in only 10.9% of eyes. IOP increases that occurred were considered manageable with standard treatments, according to the study authors.