Key Biscayne, FL—Early results from the Systemic Avastin for Neovascular Age-Related Macular Degeneration (SANA) Study showed that bevacizumab (Avastin, Genentech) improved vision and substantially reduced leakage from abnormal blood vessels in eyes of patients with neovascular (wet) age-related macular degeneration (AMD), said Philip Rosenfeld, MD, PhD.
Improvements in visual acuity were discernible within a week of the first intravenous infusion in a cohort of nine patients, said Dr. Rosenfeld, principal investigator of the SANA Study. These preliminary findings from the SANA Study were presented at the annual meeting of the Macula Society in February. He discussed outcomes for the initial group of patients through 3 months. Eighteen patients are currently enrolled in the study, and updated data were released at the Association for Research in Vision and Ophthalmology annual meeting. To date, the 3-month data with the first 18 patients are even better than the data obtained with the first nine patients, said Dr. Rosenfeld.
Most of the patients had bilateral wet AMD, and overall average vision improved in both eyes, according to Dr. Rosenfeld, associate professor of ophthalmology, Bascom Palmer Eye Institute, University of Miami School of Medicine. At 3 months, average visual acuity improved by just over two lines in the study eyes (p = 0.008) and just over three lines in the fellow eyes (p = 0.012) as measured on the ETDRS eye chart.
Bevacizumab is a recombinant humanized antibody to vascular endothelial growth factor (VEGF) and designed to bind to and inhibit VEGF, a protein that plays a critical role in angiogenesis such as the neovascularization associated with neoplasms and AMD. It is one of several anti-VEGF drugs being studied for their potential in treating AMD.
"We want a treatment that improves vision and is predictable, durable, and safe," Dr. Rosenfeld said. "Right now, based on the early Avastin results, it appears that it improves vision and is predictable and durable through 6 months. The only issue we don't know about is the safety."
The SANA Study was sponsored by and conducted at the Bascom Palmer Eye Institute. The original protocol called for infusions given every 2 weeks, which is the protocol followed when the drug is used in oncology cases. Bevacizumab received FDA approval in February 2004 for the treatment of first-line metastatic cancer of the colon or rectum in combination with intravenous 5-fluorouracil (5-FU)-based chemotherapy.
Following the FDA's action, Bascom Palmer investigators received approval from their institutional review board to study the off-label use of bevacizumab for treatment of wet AMD, Dr. Rosenfeld said.
While the investigators began with the oncology protocol, they noticed such dramatic improvement in their patients that they amended the protocol from six infusions to three, and then to two infusions. Of the first nine patients, seven received three infusions, and two were given two infusions. An additional nine patients have also received two infusions.
Re-treatments and safety Re-treatment ultimately will be necessary, although it is not yet known how frequently. Some patients in the SANA Study have done well without additional infusions for more than 6 months, Dr. Rosenfeld reported. "We certainly don't have to treat more than twice at baseline and maybe just once," he added.
At this early stage of the investigation, one of the foremost concerns is the safety of bevacizumab in patients with wet AMD, Dr. Rosenfeld said. Side effects such as an increased risk of stroke or heart attack and elevation of blood pressure were observed in oncology studies, but it is unclear whether patients with AMD-who do not have cancer, are not undergoing chemotherapy, and receive fewer doses of the drug-would face the same risk. "It is assumed that the risk would be less," he added.