CLINICAL TRIAL SPOTLIGHT

Can Radiation Help to Eradicate AMD?

NeoVista will test a combination of beta radiation and ranibizumab.

ANDREW E. MATHIS, PhD, MEDICAL EDITOR

Having just presented on March 12 the 6-month clinical data from a concomitant study on intravitreal radiation in conjunction with bevacizumab (Avastin, Genentech) for the treatment of age-related macular degeneration (AMD), NeoVista, Inc. (Fremont, Calif), has announced impending enrollment for a new AMD trial. The trial will be called Choroidal Neovascularization (CNV) Second to AMD Treated With Beta Radiation Epiretinal Therapy, or CABERNET.

At the center of both the earlier NVI-111 study and the CABERNET study is NeoVista’s Epi-Rad₉₀ Ophthalmic System, which delivers 24 gray years (Gy) of strontium 90 beta radiation. Retinal Physician spoke to Eugene de Juan, MD, the Jean Kelly Stock Professor of Ophthalmology at the University of California-San Francisco and co-inventor of the Epi-Rad₉₀, about the use of radiation in treating AMD and what the CABERNET study hopes to show.

Dr. de Juan notes that the use of radiation to treat AMD it not new. “A lot of radiation trials have been done with other forms of radiation,” he says, “The basic mechanism of action is similar to cancer therapy in that the radiation disrupts the damaged DNA and therefore prevents effective growth of rapidly turning over cells — in this case, blood vessels.”

“With other trials,” Dr. de Juan continues, “the clinical benefits have been relatively limited. It’s hoped that beta radiation and the way that it’s delivered will have a better visual effect, and certainly, so far, it seems to have a stronger biologic effect and a very positive visual effect.”

The key issue, then, is how beta radiation differs from other forms of therapeutic radiation. Dr. de Juan explains, “Beta radiation is a low-energy electron vs a gamma ray or an X-ray, which are high-energy photons. Gamma rays and X-rays use very high energy and they can be shot through the deep tissues. They are very high energy. Beta radiation is an extremely low energy. It only goes for about a quarter of an inch in air, and in water even less. It’s extremely weak in terms of energy. You could deliver the same load of radiation, but it really isn’t equivalent, because it’s a different isotope being used — strontium rather than uranium. It’s a weak beta radiation.”

Dr. de Juan continues, “Having said that, it seems that the beta-radiation source empirically works better. There’s no question that it’s safer and easier to use, but most importantly, the efficacy on CNV seems to be better.”

Vitrectomy must be performed before the beta radiation can be administered to the macula. Thus it becomes extremely important to make sure the device is properly placed. “The main reason that we do vitrectomy in this procedure is to safely place the radiation probe,” Dr. de Juan says, “so it really has to do with the safety of where we’re placing the radiation.”

The other key element to the CABERNET trial is concomitant administration of ranibizumab (Lucentis, Genentech) in two-thirds of the approximately 450 patients who will be enrolled in this randomized, prospective, controlled study. The other third will be treated with ranibizumab only. NeoVista is shooting for early to mid-April to commence enrolling patients in CABERNET.

Three earlier trials have been performed using the Epi-Rad₉₀; the first 2 trials administered radiation alone, while the other study, the results of which are mentioned above, included concomitant administration of bevacizumab.

The key way in which CABERNET will differ from the NVI-111 study is that ranibizumab will be used instead of bevacizumab. This raises questions regarding widespread off-label use of ranibizumab in treating AMD and the current high cost of ranibizumab (average annual cost of nearly $5000). Once the Food and Drug Administration (FDA) approves the Epi-Rad₉₀, will ophthalmologists use bevacizumab with the device instead of ranibizumab to save costs?

Dr. de Juan responds, “The way these devices are labeled is based very precisely on how the clinical trials were performed. So if the trial was performed with Lucentis, the labeling will say ‘Lucentis.’ Clinical use, however, will be up to the physician. A good percentage of physicians are opting for Avastin in treating AMD, although they have access to Lucentis.” He predicts that this trend will continue among users of the Epi-Rad₉₀. RP