In November, the US Food and Drug Administration granted approval for aflibercept (Eylea, Regeneron) for use in the treatment of wet age-related macular degeneration (AMD).1 This decision was largely based on the 1-year data obtained in the VIEW 1 and VIEW 2 studies, which showed that aflibercept injected every 8 weeks was clinically equivalent to Lucentis (ranibizumab, Genentech) injected every 4 weeks for maintaining visual acuity (less than 15 letters of vision loss) over 52 weeks.2,3 This decrease in frequency of dosing is obviously desirable.
The 2-year data from these studies, released 1 week after FDA approval was received, tell a somewhat different story, but still show promise for aflibercept. The data show that over the course of the second year, patients in the aflibercept group required an average of 0.5 fewer injections than patients in the ranibizumab group (4.2 vs 4.7), while achieving very similar results in visual acuity (7.9 letter gain for ranibizumab vs 7.6 letters for aflibercept). The study, however, was not designed to determine the difference between aflibercept and ranibizumab. Only by performing a true asneeded (prn) study can a good comparison be made. VIEW was more of a pseudo-prn study in which all patients received injections at least once every 3 months, but more frequent injections were allowed if needed.
The mechanism of action for aflibercept is slightly different other anti-VEGF agents in that its soluble receptor binds to VEGF and also to platelet-derived growth factor. Aflibercept binds not only to a wider spectrum of molecules, but it binds with a higher affinity. How significant this difference is may be questionable, as the affinities of ranibizumab and bevacizumab (Avastin, Genentech) are already quite high.
Although I have begun using aflibercept in my practice since its approval, the issues of reimbursement and assignment of a J code must be addressed before I adopt this drug on a widespread basis. When ranibizumab was first approved, many clinicians experienced a large backlog of unpaid claims during the waiting period for that J code, and I do not want to have the same thing happen with aflibercept, particularly when we have a good anti-VEGF treatment at our disposal for which we can be reimbursed. Regeneron, however, has been proactive in providing information to help identify insurance companies that will cover the drug prior to the J code assignment.
Many of my patients have been receiving injections of ranibizumab or bevacizumab either monthly or every 6 weeks and still have had persistent fluid on optical coherence tomography (OCT). For these patients, aflibercept will offer an advantage with less frequent dosing.
The lower cost of aflibercept, particularly because its label calls for less frequent dosing, is quite remarkable. In my opinion, this strategy will prove to be a game-changer in terms of how new drugs are brought to market in the future.
Philip J. Rosenfeld, MD, PhD, is Professor of Ophthalmology at Bascom Palmer Eye Institute, University of Miami, Miller School of Medicine, Miami. He is a member of the Retina Today Editorial Board. Dr. Rosenfeld states that he has no financial interests or relationships to disclose. He may be reached at +1 305 326 6148; or via email at prosenfeld@med.miami.edu.
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