CLINICAL TRIAL SPOTLIGHT

Implant May Reduce Ranibizumab Injections

Alimera believes Medidur FA can be a powerful adjunct to ranibizumab therapy.

ANDREW E. MATHIS, PhD, MEDICAL EDITOR

Alimera Sciences (Atlanta) announced that it has begun enrollment in a pilot study to determine the safety and efficacy of the Medidur fluocinolone acetonide (FA) intravitreal insert in conjunction with ranibizumab (Lucentis, Genentech) for patients with neovascular age-related macular degeneration (AMD). While Medidur FA has been tested extensively for diabetic macular edema (DME), this is the first time the insert will be evaluated for wet AMD.

Ken Green, PhD, senior vice president and chief scientific officer at Alimera, explained to Retinal Physician the thinking behind using this combination of an inhibitor of vascular endothelial growth factor (VEGF) and a corticosteroid. "Among other things, corticosteroids suppress VEGF secretion at a transcriptional level," Dr. Green said. "Therefore, the thinking is, if a VEGF antibody has removed the "free" VEGF from the system, a therapy that suppresses future VEGF secretion may retain the established benefit."

The trial, dubbed the Medidur FA for AMD Pilot (MAP) study, is designed to enroll 30 patients, with half randomized to an arm receiving a 0.2-μg/day insert and the other half receiving an insert releasing 0.5 μg/day. Dr. Green pointed out that these were the same doses compared in the FAME phase 3 study that tested the Medidur FA insert in patients with diabetic macular edema.

DOSING SCHEDULES

"The high dose of Medidur FA is designed to release drug over an 18- to 24-month period," Dr. Green said, "and the low dose is designed to release drug over a 24- to 30-month period, with therapeutic effect to be determined in clinical trials. In this trial, patients will be randomized to either the high or low dose at baseline and followed for 3 years. There will be no retreatments."

As with many other AMD trials, the MAP study will endeavor to determine whether the number of ranibizumab injections given to a patient can be reduced, in this case by supplementing the injections with fluocinolone acetonide. "The goal is to maintain the effect established with ranibizumab, but dramatically reduce the need for ranibizumab injections post-Medidur FA insertion," Dr. Green said. Asked about other study endpoints, Dr. Green replied, "Given that this is a phase 2 exploratory study, we will look at many endpoints to assess effectiveness, including change from baseline in mean visual acuity and number of ranibizumab injections needed post-Medidur FA insertion vs pre-Medidur FA insertion. Success will be defined as a very significant reduction in ranibizumab use, with retained benefit."

With other corticosteroid implants either on the market or in development, we asked Dr. Green why fluocinolone might be superior to, for instance, triamcinolone acetonide, in reducing the number of ranibizumab injections and for the treatment of AMD in general. "We are not claiming that the corticosteroid FA is superior to triamcinolone or dexamethasone with respect to VEGF suppression," Dr. Green said. "Since the goal is to reduce the frequency of intravitreal injections in patients being treated with ranibizumab, and since FA is the only corticosteroid formulated in a dosage form (Medidur FA) that releases drug over a period of years, we believe Medidur FA represents the most attractive corticosteroid dosage form to study for concomitant use with ranibizumab in the treatment of wet AMD."

WHERE IT ENDS

Finally, asked whether he sees a primary role for corticosteroid implants in the treatment of AMD, Dr. Green said, "At this time, we do not foresee administration of Medidur FA as precluding the use of other treatments for wet AMD or as becoming first-line therapy for wet AMD. We will explore this further, though, if Medidur FA becomes a marketed product. However, we do see this becoming first-line therapy for DME if Medidur FA receives FDA approval for treatment of DME." RP