The regulatory process for much-ballyhooed Macugen is under way.

Partners Eyetech Pharmaceuticals Inc. and Pfizer Inc. completed their submission of a new drug application with the FDA, applying for use of the potential blockbuster in wet age-related macular degeneration. Filed as a rolling NDA, the companies submitted the final section of the application ahead of a previously publicized third-quarter goal. And for New York-based Eyetech, the submission represents yet another seminal event for the company this year.

"When we set our goals back in January, when we did our IPO, one of the key goals for the year was to complete the NDA filing," Glenn Sblendorio, Eyetech's chief financial officer, told BioWorld Today. "This is obviously the completion of another step in the process of getting Macugen approved."

Eyetech's initial public offering was the first biotech IPO this year, through which it raised $136.5 million in gross proceeds. The stock priced at $21 per share and rose to $32.40 by the end of the day. It hasn't looked back since - on Thursday, Eyetech's stock (NASDAQ:EYET) added another $2.01 to close at $45.90. (See BioWorld Today, Feb. 2, 2004.)

Such investor optimism stems from the promise of Macugen (pegaptanib sodium injection), an anti-angiogenesis product that inhibits the activity of vascular endothelial growth factor (VEGF) as a pegylated anti-VEGF aptamer.

The product has fast-track designation, and the NDA is part of the FDA's Pilot 1 program that allows for complete review of individual units within six months of submission and provides early feedback on pre-submissions. The FDA's Dermatologic and Ophthalmic Drugs Advisory Committee is scheduled to review Macugen on Aug. 27.

Looking optimistically at the approval process, Sblendorio said the partners could get the product onto the market early next year.

"At this point, we're not changing our guidance," he said. "We had said the first half of '05, and if you add six months for the fast-track process, that gets us to the end of the year."

Sblendorio said the application's preclinical and clinical sections already have been accepted by the FDA, and the companies provided the chemistry, manufacturing and controls section last. He declined to detail data submitted to the agency as part of the NDA, but prior late-stage clinical trials have demonstrated Macugen's potential.

Use of the drug proved statistically significant in the primary endpoints of two Phase II/III trials, one of which included 578 wet AMD patients and another in 612 patients, in the proportion of patients losing less than 15 letters of visual acuity from baseline after 54 weeks. AMD cases include three subtypes - predominantly classic, minimally classic and occult - and Macugen showed a consistent treatment effect in all three subtypes of wet AMD.

Pfizer also realized the promise of Macugen and signed on as a development partner a year and a half ago. The deal could be worth $750 million to Eyetech, through which it and Pfizer, also of New York, would co-market the product in the U.S. and share all profits. Pfizer has exclusive rights to develop and commercialize Macugen overseas. (See BioWorld Today, Dec. 19, 2002.)

"We're still working with our partner Pfizer to define our own [sales] projections," Sblendorio said. "Now, with this filed, the commercial teams are in full swing, and I think we'll give further guidance and updates on [launch plans] as we move through the year."

He said the original decision to partner was born of a need for commercial capabilities, noting that Pfizer provides marketing capacity and both companies would have all pieces in place for launch.

If approved, its chief competitor would be Visudyne, made by QLT Inc., of Vancouver, British Columbia. Visudyne was approved in 2000 to treat the classic form of wet AMD. Other potential competitors include two products in Phase III development, another anti-angiogenesis product called Lucentis from South San Francisco-based Genentech Inc. and a modified steroid called Anecortave Acetate from Fort Worth, Texas-based Alcon Research Ltd.

Development of Macugen continues in Phase II programs in retinal vein occlusion and diabetic macular edema, for which the product also has FDA fast-track designation. Findings from a recently completed diabetic macular edema study showed positive visual and anatomical outcomes, and Sblendorio said the partners are mapping out a Phase III trial design to begin early next year.

Beyond its Macugen programs, Eyetech expects to broaden its development portfolio through a recently signed deal with Archemix Corp., of Cambridge, Mass. (See BioWorld Today, April 15, 2004.)

"That gives us access to some aptamer technology," Sblendorio said, "and that will be the building block for some early stage opportunities that we'll keep you posted on."

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