Exudative age-related macular degeneration update: Phase II study outcomes encouraging for combination therapy treatment

When data were analyzed from 25 patients who reached the 18-month visit in a phase II trial evaluating epiretinal brachytherapy (EpiRad90 Ophthalmic System, NeoVista) with bevacizumab (Avastin, Genentech), they demonstrated that the novel combination was associated with a significant gain in vision, an acceptable safety profile, and with minimal need for additional anti-VEGF treatment beyond an initial two injections.

Key Points

Scottsdale, AZ-A dual regimen combining epiretinal brachytherapy (EpiRad90 Ophthalmic System, NeoVista) with bevacizumab (Avastin, Genentech) appears to be a safe and effective approach for treating exudative age-related macular degeneration (AMD), with an advantage for minimizing the need for further intravitreal injections of anti-vascular endothelial growth factor (anti-VEGF) therapy, according to 18-month results from a phase II study.

Nelson R. Sabates, MD, reported the outcomes from the clinical trial here at the annual meeting of the Retina Society. He is professor and chairman, Department of Ophthalmology, University of Missouri-Kansas City School of Medicine, Kansas City.

Designed as a feasibility study and sponsored by NeoVista, it enrolled 34 patients (mean age, 72 years) at two centers in Brazil and Mexico. All angiographic lesion types (predominantly classic, minimally classic, occult with no classic) were represented in the series. All patients received a single 24-Gy treatment of epiretinal brachytherapy plus two intravitreal injections of bevacizumab administered either prior to or simultaneously with radiation and then 1 month later. The investigators were allowed to use their discretion in administering additional injections of the anti-VEGF agent based on their evaluation of disease activity.

More than two-thirds of patients received no further bevacizumab injections, whereas among the patients who were treated again, only 2.4 additional injections had been given on average.

"We've seen important advances in pharmacotherapy for exudative AMD, but the search continues for the best modality or combination therapy," Dr. Sabates said. "Epiretinal brachytherapy plus intravitreal anti-VEGF injection targets both established vessels and an inciting factor for new vessel growth, and [it] appears to be a promising combination based on its efficacy and safety. This dual treatment appears to induce more rapid regression of the neovascular membrane and, importantly, has minimized the need for intravitreal injections."

The epiretinal brachytherapy allows focal delivery of beta radiation directly to the neovascular membrane, sparing the normal retinal vasculature. A sealed radiation source containing strontium-90 temporarily is placed over the target tissue using a hand-held medical device in a procedure involving standard vitreoretinal surgical techniques. The radiation targets an area up to 3 mm deep and up to 5.4 mm wide.

The findings from safety monitoring in the phase II trial also have been very encouraging, according to Dr. Sabates. Most of the adverse events were related to the vitrectomy procedure, but none were unusual.

"So far, with follow-up of up to 2 years available in some patients, there is no evidence of radiation retinopathy, which would have certainly manifested after use of conventional radiotherapy techniques," he said.

Dr. Sabates is the lead investigator for an ongoing NeoVista-sponsored phase III study evaluating concomitant epiretinal brachytherapy and intravitreal anti-VEGF therapy. Known as CABERNET (CNV Secondary to AMD Treated with BEta RadiatioN Epiretinal Therapy), it is an international, multicenter, open-label, active-controlled study aiming to enroll 450 subjects at 45 investigational sites. Patients with all AMD-related CNV lesion types are eligible as long as they are treatment naïve, the total lesion size is <12 disc areas, and the greatest linear dimension is ≤5.4 mm. They are being randomly assigned to receive concomitant treatment with epiretinal brachytherapy plus two injections of ranibizumab (Lucentis, Genentech) or ranibizumab alone, given monthly for 3 months and then once every 3 months. Patients in either arm are eligible for additional injections of ranibizumab when they return for their monthly follow-up visits.

The study was launched in April 2007, and the first patient enrolled in that study was treated by Dr. Sabates. At the end of September 2008, about 200 patients had received their initial treatment. The primary efficacy assessment will be performed at 12 months.

"The results of this pivotal trial will provide the definitive answer of whether epiretinal brachytherapy will become part of our armamentarium for the treatment of exudative AMD," he concluded.

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