The FDA authorized the first anti-angiogenic treatment for ophthalmology, Macugen, which received approval for the treatment of neovascular (wet) age-related macular degeneration.
The drug, developed in concert by Eyetech Pharmaceuticals Inc. and Pfizer Inc., helps preserve vision and helps limit progression to legal blindness. Its approval follows a priority review under the FDA's rolling submission-Pilot 1 program.
"Macugen represents an important paradigm shift in the treatment of this devastating disease," said Eyetech CEO David Guyer, noting that the theory behind the drug's therapeutic approach has roots that date back 35 years. "It's a novel treatment that's based on elegant science."
Macugen (pegaptanib sodium injection) is the first in a new class of ophthalmic drugs to specifically target vascular endothelial growth factor (VEGF), a protein that acts as a signal in triggering the abnormal blood vessel growth and leakage that characterize wet age-related macular degeneration (AMD). Specifically, the pegylated aptamer binds to VEGF 165, a protein that plays a role in angiogenesis and increased permeability, or leakage from blood vessels.
"What's very important about Macugen," Guyer told BioWorld Today, "is that it targets the underlying biology of the disease, and we have a label for 100 percent of patients with neovascular AMD."
The approval triggered a $90 million license fee payment to Eyetech from Pfizer, which also is due to make an additional $15 million investment in Eyetech's common stock within 35 business days. On Monday, Eyetech's stock (NASDAQ:EYET) lost $2.29 to close at $43.21.
The drug is administered in a 0.3-mg dose once every six weeks by intravitreal injection. The partners, both of which are based in New York, plan to launch it next quarter.
Macugen is the first therapy indicated for the treatment of all types of wet AMD, regardless of lesion subtype or size. Previously, the only FDA-approved treatment, Visudyne (verteporfin, QLT Inc. and Novartis AG), was limited to the predominantly classic subtype of wet AMD. That accounts for about 25 percent of the wet AMD patient population, but it still generated $357 million in sales last year.
"From our perspective, the fact that the FDA has approved the all-wet AMD label is one way to assure that patients have access to the drug," Paul Chaney, Eyetech's chief operating officer, told BioWorld Today. "And physicians know that they're being reimbursed for the delivery of the drug for the patients they feel are appropriate and can benefit from the treatment."
In the U.S., more than 1.6 million of the estimated 15 million AMD patients have the active blood vessel growth and blood vessel leakage associated with wet AMD. There are more than 200,000 new cases of wet AMD diagnosed each year, and Eyetech and Pfizer expect that number to increase as baby boomers age and overall life expectancy increases.
Neither company has disclosed sales goals or the product's cost, though Chaney said a price soon would be determined. Terms of the relationship between Eyetech and Pfizer call for the companies to co-promote the product in the U.S., with the former fielding about 60 employees as sales representatives and reimbursement consultants for retinal specialists. Pfizer will send out a sales team of about 160 people to ophthalmologists and optometrists.
"The goal is to focus the majority of our efforts, from a product distribution and access perspective, to retinal specialists who are really at the center of AMD treatment," Chaney said. "We also want to reach out to the general ophthalmology and optometry practices, so they know there is a new treatment available to offer something that is effective and safe for their patients, and then direct them to retina specialists, who will be the ones that really drive the use of Macugen."
Data from the pivotal trials underlying the approval, which involved about 1,200 patients with all subtypes of wet AMD, showed that 70 percent of Macugen-treated patients lost less than three lines of vision acuity on the eye chart by week 54, the primary efficacy endpoint, compared to 55 percent of control-treated patients (p<0.0001).
The approval follows an FDA panel review in which no vote was taken, but allowed the agency's Dermatologic and Ophthalmic Drugs Advisory Committee to discuss the rolling new drug application submitted over the summer under fast-track and priority-review guidelines. (See BioWorld Today, June 18, 2004, and Aug. 30, 2004.)
The drug is being reviewed in Europe and Canada, under the direction of Pfizer, which has the lead role in advancing Macugen outside the U.S. The drug also has completed bridging studies in Japan.
Its approval also benefited three other companies that had ancillary roles in Macugen's development, said Glenn Sblendorio, Eyetech's chief financial officer and senior vice president of finance. The primary license to Macugen comes from Gilead Sciences Inc., of Foster City, Calif. Isis Pharmaceuticals Inc., of Carlsbad, Calif., said it earned a $3 million milestone payment from Eyetech. Also, Nektar Therapeutics provides Eyetech with PEGylation technology for use in Macugen. Nektar, of San Carlos, Calif., sub-licenses the PEG technology from Enzon Pharmaceuticals Inc., of Bridgewater, N.J.
Macugen also is being studied for the treatment of diabetic macular edema and retinal vein occlusion, and Eyetech recently acquired a manufacturing facility to aid in its production. (See BioWorld Today, Nov. 16, 2004.)
Positive Phase II data on the drug's use for diabetic macular edema were reported earlier this year, and Phase II enrollment is under way in a retinal vein occlusion study. The FDA has given the diabetic program fast-track status.
Beyond Macugen, Eyetech owns exclusive rights for the use of aptamers in all ophthalmic targets as a result of a deal with Archemix Corp., of Cambridge, Mass. Preclinical development is focused on the identification of back-of-the-eye targets to develop aptamer-based drugs, and on drug delivery technology. (See BioWorld Today, April 15, 2004.)
But Macugen is the centerpiece of Eyetech, which earlier this year completed a $136.5 million initial public offering, four years after its founding.
"It has been a great year," Guyer said, "with the IPO at the beginning of the year and this approval to end it being great bookends."