Analysis of 6-month interim data from the RADICAL (Reduced Fluence Visudyne Anti-VEGF-Dexamethasone In Combination for AMD Lesions) triple and double therapy study suggests that the treatments are safe, with similar efficacies found across the four treatment arms, according to lead investigator Allen C. Ho, MD, Co-chairman of the RADICAL study. Dr. Ho is a Professor of Ophthalmology at Thomas Jefferson University Retina Service and Wills Eye Hospital in Philadelphia, practitioner at Mid Atlantic Retina, and Chief Medical Editor of Retina Today.

Dr. Ho outlined the following 6-month results of the study in an interview with Retina Today.

WHAT IS THE RADICAL TRIAL?
The RADICAL study is a prospective, multicenter, randomized clinical trial investigating combination therapy for the treatment of patients with choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD). The purpose of the study is to determine if combination therapy reduces retreatment rates compared with ranibizumab monotherapy while maintaining similar visual acuity outcomes and an acceptable safety profile.

The trial, sponsored by QLT Inc. (Vancouver, British Columbia, Canada), includes 162 patients randomized to one of four treatment arms: double therapy of photodynamic therapy (PDT) with reduced-fluence verteporfin (Visudyne; Novartis) followed by ranibizumab (Lucentis, Genentech; n=43), reduced-fluence PDT with verteporfin followed by ranibizumab-dexamethasone triple therapy (n=39), very low-fluence PDT with verteporfin followed by ranibizumab-dexamethasone triple therapy (n=39), or ranibizumab monotherapy (n=41).

DOSING SCHEDULE
RADICAL will follow patients for 24 months. After initial treatment, patients in the combination therapy groups undergo monthly evaluation. Combination retreatment is not administered more frequently than every 2 months. If retreatment is needed in an intervening month, the patient will receive ranibizumab injection only. Patients in the ranibizumab monotherapy group receive mandatory retreatment at months 1 and 2; subsequent retreatment is as needed. In all treatment arms, monthly assessment with potential retreatment will continue through 12 months. Between 12 and 24 months, patients will be assessed every 3 months, or more frequently at the investigator's discretion.

SIX-MONTH RESULTS
At 6 months, best corrected visual acuity increased similarly among the treatment groups, with a mean 4.55 letter improvement across the four arms. Seventy-four percent of patients in the ranibizumab monotherapy group and 68% (mean) of patients in the combination therapy groups experienced an increase in letters of visual acuity. Fifteen or more letters of visual acuity were gained at month 6 by 18% of ranibizumab monotherapy patients and 20.6% (mean) of patients receiving combination therapy.

Combination therapy regimens in this study appear safe at this time. Three patients had a serious ocular event associated with treatment, including increased IOP, retinal tear, and decreased vision. These patients were in the reduced-fluence verteporfin followed by ranibizumab-dexamethasone triple therapy and the very low-fluence verteporfin followed by ranibizumab-dexamethasone triple therapy groups. There were no cases of endophthalmitis.

Although cumulative retreatment rates were lower in all combination groups compared with the ranibizumab monotherapy group, this was influenced by the mandatory retreatments at months 1 and 2 in the ranibizumab monotherapy group. Longer-term follow-up is needed to better compare the retreatment rates in each group.

"The 6-month RADICAL combination therapy study for AMD supports the safety of combination treatments for this condition. These results are preliminary and we need further follow-up to determine whether there will be a reduced need for retreatments using combination therapy," Dr. Ho said in the interview. "The Data and Safety Monitoring Committee recommends continuation of this study. We are excited about the potential of combination therapy for AMD."

Basic inclusion and exclusion criteria, as well as study information and study centers, are outlined at www.clinicaltrials.gov/ct2/show/NCT00492284.