Bevacizumab versus ranibizumab: either way, patients win

New Orleans-Intravitreal medical therapy for age-related macular degeneration (AMD) is dominated by the two anti-vascular endothelial growth factor (VEGF) drugs, ranibizumab and bevacizumab (Lucentis and Avastin, respectively, Genentech). They both appear very similar in their ability to increase visual acuity and stabilize vision in patients with AMD. Cost currently seems to be affecting physicians' choices between the two, but the results of two comparison studies may settle the question of which drug is more efficacious, according to Philip J. Rosenfeld, MD, PhD, who spoke at the American Academy of Ophthalmology annual meeting.

"The advances of the last 12 years have been dramatic in our ability to treat neovascular AMD. Up to about 6 years ago, we could only slow the vision loss, but now in the age of 'Luvastin' we actually started to see vision improve starting in 2001," he said. Dr. Rosenfeld is professor of ophthalmology, Bascom Palmer Eye Institute, University of Miami School of Medicine.

Along with this improvement in vision has been a dramatic increase in the number of intravitreal injections performed as well as in the use of optical coherence tomography (OCT) to document and study those changes in the retinal anatomy. "This has been a dramatic paradigm shift in our ability to care for patients and it has created significant stresses on the delivery of patient care," he noted.

Ranibizumab, bevacizumab, and the VEGF trap, the last of which is currently in phase 3 trials, are the available agents that can target the extracellular VEGF in the eye.

"The biggest differences between ranibizumab and bevacizumab are in their sizes and affinity. Both are derived from the same mouse monoclonal antibody and they have been humanized. The antibody-binding fragment ranibizumab was genetically affinity-matured so that its binding affinity is from 5- to 20-fold higher compared with the bevacizumab affinity for VEGF. Bevacizumab is the larger molecule, but it is also substantially cheaper ($5.50 per mg for bevacizumab versus $4,000 per mg for ranibizumab)," he noted.

The 1-year results of the ANCHOR and the 2-year MARINA studies provided the basis for the FDA approval of ranibizumab to treat wet AMD. The importance of the minimally classic and occult AMD data from the MARINA study was that for the first time there was an increase in average visual acuity during the first 3 months of treatment that was sustained over 24 months. This difference achieved in the treatment versus the sham treatment groups amounted to 20 to 21 letters of vision, depending on the dose of the drug.

The 2-year results from the ANCHOR study in which ranibizumab was compared with verteporfin photodynamic therapy (Visudyne, Novartis Ophthalmics) showed that there was an 18- to 20-letter difference in vision using ranibizumab, depending on the dose of the drug.

The PRONTO study was carried out at the Bascom Palmer Eye Institute to look at alternative dosing regimens for ranibizumab with the goal of avoiding monthly intravitreal injections for 2 years or longer. Initially, the patients received injections at baseline, and months 1 and 2; any subsequent injections were based on need (i.e., changes in central retinal thickness) as determined by OCT.

"On average the patients in the PRONTO study received 10 intravitreal injections over the 2 years of the study, with most patients getting three to nine injections. Of the 40 patients, only two patients required injections almost on a monthly basis," Dr. Rosenfeld reported.

When the investigators compared the results from the ANCHOR, MARINA, and PRONTO studies, the results were similar for the ranibizumab dose of 0.5 mg.