Systemic, intravitreal therapy encouraging for neovascular AMD

October 1, 2005

Montreal—Favorable functional and anatomic outcomes in eyes with subfoveal neovascular age-related macular degeneration (AMD) were reported following 24 weeks in an open-label, uncontrolled clinical trial using off-label, systemic and intravitreal therapy with bevacizumab (Avastin, Genentech), a humanized full-length monoclonal anti-VEGF antibody.

The exploratory investigation, which is named the Systemic Bevacizumab (Avastin) Therapy for Neovascular Age-Related Macular Degeneration (SANA) study, was undertaken at the Bascom Palmer Eye Institute, University of Miami School of Medicine. Eighteen eligible patients received two or three doses of bevacizumab, 5 mg/kg administered at 2-week intervals, reported Philip J. Rosenfeld, MD, PhD, at the annual meeting of the American Society of Retina Specialists.

The study participants were patients with neovascular AMD for whom no other treatment was available at the time of study initiation.

Rapid VA improvements

Assessments performed through 24 weeks of follow-up showed the treatment resulted in rapid improvements in VA as well as in angiographic (fluorescein and indocyanine green) and OCT outcomes. Ten patients developed mild hypertension, but it was easily controlled, and there have been no serious side effects.

"This is just a small, open study and while the results are promising, it cannot answer the question of whether the benefits of this systemic Avastin therapy outweigh its risks with respect to thromboembolic events," said Dr. Rosenfeld, associate professor, Bascom Palmer Eye Institute, University of Miami School of Medicine, Miami. "Bevacizumab, when used to treat metastatic colorectal cancer with every 2-week dosing for many months, does have higher systemic risks than any of the other drugs currently used to treat neovascular AMD, but we don't know the true risks in the setting of non-oncology patients receiving two or three doses over 6 months. Addressing that issue would require a study enrolling hundreds of patients."

Bevacizumab is currently approved for the treatment of metastatic colorectal cancer to be used in conjunction with 5-fluorouracil chemotherapy. It is recommended to be administered every 2 weeks.

Dr. Rosenfeld and his colleagues became interested in investigating bevacizumab based on their positive premarketing clinical trial experience with intravitreal ranibizumab (Lucentis, Genentech). Ranibizumab is a derivative of the full-length antibody bevacizumab and is further modified to increase its affinity for vascular endothelial growth factor (VEGF). Both bevacizumab and ranibizumab bind all biologically active isoforms and proteolytic fragments of VEGF.

In the SANA study, the 18 participants were enrolled in two cohorts with the first nine patients followed for 3 months to evaluate safety concerns prior to entry of the second group of patients. One eye in each patient was designated as the study eye at baseline. Mean VA for the study eyes was 20/80; 16 patients had a history of CNV in the fellow eye and mean VA for the fellow eyes was 20/160.

All patients received two doses of bevacizumab, while a third dose was given at week 4 only if there was evidence of recurrent CNV. Due to the potential risks, patients were followed very closely. Visits were scheduled weekly for the first 6 weeks, biweekly for the next 6 weeks, and then monthly. Efficacy assessments included vision and OCT at every visit, fluorescein angiography every month, and ICG angiography every 3 months.

The data from the 18 patients showed there was an improvement in VA of 7 letters by week 1 and 13 letters by week 24. Accompanying the vision improvement was a decrease in central retinal thickness of 115 μm at week 1, and by week 24, the central retinal thickness remained 112 μm lower than baseline.