FDA Approves Aflibercept for Age-Related Macular Degeneration

Caroline Helwick

Disclosures

November 18, 2011

November 18, 2011 — The US Food and Drug Administration (FDA) today approved aflibercept ophthalmic solution (Eylea, Regeneron Pharmaceuticals Inc) for the treatment of neovascular ("wet") age-related macular degeneration (AMD).

"Eylea is an important new treatment option for adults with wet AMD," said Edward Cox, MD, MPH, director of the Office of Antimicrobial Products in FDA's Center for Drug Evaluation and Research. "It is a potentially blinding disease and the availability of new treatment options is important."

The recommended dose is 2 mg every 4 weeks (monthly) for the first 12 weeks, followed by 2 mg every 8 weeks (2 months), according to a Regeneron news release. The company plans to make the drug available to patients "within the next few days," according to Regeneron president and chief executive officer Leonard S. Schleifer, MD, PhD.

In August, the FDA pushed back its target date for completing its review of aflibercept. According to the manufacturer, they needed more time to review recent responses as part of Regeneron's bid to obtain a license for AMD, the company indicated.

The approval follows a unanimous recommendation for approval on June 17 by the FDA's Dermatologic and Ophthalmic Drugs Advisory Committee.

"We are very excited about the approval of this drug," aflibercept trial investigator David S. Boyer, MD, clinical professor of ophthalmology at the University of Southern California Keck School of Medicine, Los Angeles, told Medscape Medical News. "We know that with AMD drugs, 1 size does not fit all. Ranibizumab (Lucentis, Genentech) and bevacizumab (Avastin, Genentech) are excellent drugs, but there are patients who do not have an optimal response to them. This drug may offer an incredible ability to dry these patients out and improve their vision."

Aflibercept, an injectable drug, is a highly potent blocker of vascular endothelial growth factor (VEGF) and placental growth factor. VEGF's normal role is to trigger formation of new blood vessels supporting growth of bodily tissues, but in AMD it is also associated with the growth of abnormal new blood vessels in the eye that exhibit vascular permeability and lead to edema.

Philip Rosenfeld, MD, PhD, professor of ophthalmology at Bascom Palmer Eye Institute in Miami, Florida, commented, "I don't anticipate better visual acuity outcomes compared with Lucentis and Avastin, just fewer visits and fewer injections. If the use of aflibercept can decrease the need for retreatment, then this will be a win-win for patients and clinicians."

Aflibercept, also known as VEGF Trap-Eye, is a fully human fusion protein consisting of portions of VEGF receptors 1 and 2, which binds all forms of VEGF-A, along with the related placental growth factor, which the drug blocks.

Drug Was Noninferior to Standard of Care, Ranibizumab

The drug's approval was based on positive results from the 2 phase 3 VEGF Trap-Eye: Investigation of Efficacy and Safety in Wet AMD (VIEW) trials. Both found the drug noninferior to ranibizumab, the FDA-approved agent considered the most potent for the condition. In VIEW 1 (n = 1217), conducted in the United States, and VIEW 2 (n = 1240), conducted in Europe, all regimens of the drug, including 2 mg dosed every 2 months (after 3 loading doses), successfully met the primary endpoint of statistical noninferiority compared with ranibizumab, which is currently the most potent FDA-approved treatment option for wet AMD.

The proportions of patients who maintained or improved vision over the course of 52 weeks in VIEW 1 were 96%, 95%, and 95% of patients receiving aflibercept 0.5 mg monthly, 2.0 mg monthly, and 2.0 mg every 2 months, respectively. This compared with 94% of patients receiving the standard 0.5-mg monthly dose of ranibizumab.

For the secondary endpoint, visual acuity, the new drug was better. Patients receiving 2 mg monthly had a greater mean improvement in visual acuity at week 52, with a gain of 10.9 letters compared with 8.1 letters with ranibizumab (P < .01). All other dose groups were not significantly different from ranibizumab with respect to this secondary endpoint.

In VIEW 2, vision was maintained in 96% of all aflibercept dose groups and in 94% of the ranibizumab group. All doses were statistically noninferior to ranibizumab, and no differences were noted between the drugs in visual acuity gain.

More Options Desirable

George Williams, MD, spokesperson for the American Academy of Ophthalmology and director of the Beaumont Eye Institute at the William Beaumont Hospital in Royal Oak, Michigan, commented: "Ophthalmologists are excited about the potential that the VEGF Trap compound has for the management of neovascular AMD.

"This will give us another apparently effective drug. As with many complex chronic diseases, we have patients who will respond better to one than another. The more arrows in our quiver, the better," Dr. Williams said.

He found VIEW 1 and VIEW 2 to be "well conducted, designed, and executed, and to provide very strong data to tell us aflibercept is effective," he said. "The question now is where it fits in the therapeutic landscape."

Dr. Williams added that if comparable efficacy with less-frequent dosing (which kicks in after 3 months) holds up for the long term, "this will obviously be a significant advantage to patients."

Echoing the need for multiple treatment options, Dr. Boyer added: "There are anatomic 'nonresponders' who continue to leak, don't flatten out, and require more frequent injections. In some of these resistant cases, the drug can be beneficial. My hope is that because of the affinity of this drug with VEGF, which is 100 times greater than ranibizumab and 1000 [times] greater than bevacizumab, we can dry out some of these patients. And we hope this translates into improvement of vision in the long run," he said.

Because cost has been part of the debate in the treatment of this disease, with bevacizumab costing considerably less than ranibizumab, Medscape Medical News asked Dr. Boyer how aflibercept enters into this equation.

"We look at efficacy and safety first with any new drug. But we are increasingly living in a value-based world," he commented, "so the value of this drug may be ultimately driven by the cost."

Dr. Rosenfeld, who pioneered the use of bevacizumab in AMD, said, "While we don't know the cost of aflibercept yet, I am not anticipating a major cost savings from its use compared with Lucentis. My expectation is that the fewer number of injections will be factored into the anticipated higher cost of aflibercept. If aflibercept lives up to its clinical trial hype in real-world clinical practice, then I would expect aflibercept to replace Lucentis as the high-cost option, while Avastin will continue to be used as the low-cost option."

Regeneron and Bayer HealthCare are collaborating on the global development of aflibercept for wet AMD, central retinal vein occlusion, diabetic macular edema, and other eye diseases and disorders. Bayer has submitted an application for marketing authorization of the drug in Europe. Regeneron is also testing another formulation of aflibercept in colon, lung, and prostate cancer and expects data next year from those trials.

Dr. Boyer has reported receiving consultant fees from Regeneron Pharmaceuticals Inc, Genentech, Allergan, and Alcon Pharmaceuticals. Dr. Williams has received consulting fees and grant support from Alcon, Allergan, Genentech, Neurotech, Nu-Vue Technologies, OptiMedica, Pfizer, and Thrombogenics. Dr. Rosenfeld has disclosed no relevant financial relationships.

Comments

3090D553-9492-4563-8681-AD288FA52ACE
Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.
Post as:

processing....