Washington Editor

Eyetech Pharmaceuticals Inc. could gain about $750 million in a deal with Pfizer Inc. centered on development and commercialization of Macugen, Eyetech's lead drug candidate for age-related macular degeneration and diabetic macular edema.

The two disorders are leading causes of blindness, for which there are limited treatments, said officials at Eyetech, who believe the market is wide open for Macugen (pegaptanib sodium) - one factor responsible for the company's success in raising money and for signing such a lucrative deal.

And the other factor, of course, is the science under which Macugen was developed.

Macugen is an aptamer that selectively binds to and neutralizes the vascular endothelial growth factor (VEGF), the cause of age-related macular degeneration (AMD) and diabetic macular edema (DME).

The company said that in early clinical studies, Macugen has been shown to inhibit abnormal blood vessel growth and stabilize or reverse blood vessel leakage in the back of the eye. Macugen, a fast-track product, is in Phase III studies for wet AMD and Phase II studies for DME.

"Our early trials in both Phase I and Phase II have shown that approximately 26 percent of patients have gained three lines or more [on a standard eye chart], which is a significant vision improvement," David Guyer, Eyetech's co-founder and CEO, told BioWorld Today. "We've been fortunate to raise so much money and partner with such a wonderful company as Pfizer, and I think it is because of the exciting science that shows VEGF causes these diseases, and blocking VEGF can prevent these vision losses."

Indeed, Pfizer has agreed to pay Eyetech a $100 million up-front fee, with the potential for an additional $195 million in milestone payments based on worldwide regulatory submission and approvals. Eyetech also has the potential to receive up to an additional $450 million in milestone payments, contingent upon successful commercialization of Macugen and the attainment of agreed-upon sales levels.

Pfizer also will fund the majority of the ongoing development costs associated with both indications. On FDA clearance, Macugen would be co-promoted by Eyetech and Pfizer in the U.S., where Eyetech would have an ophthalmology sales force. Outside the U.S., Pfizer will market the product exclusively under a royalty-bearing license.

"A deal of this magnitude just shows that big pharma is always interested when a company has a very promising lead compound," Damion Wicker, partner and co-head of life sciences at J.P. Morgan Partners in New York, told BioWorld Today. "Some people may have felt that deals like this would no longer occur, but when you have a first-rate team with a very promising lead program backed by a blue chip group of investors, it makes it possible for one of the largest pharmaceutical companies to consider a deal like this."

J.P. Morgan invested $25 million in Eyetech as part of the company's notable $108.5 million Series C financing that closed in August. Prior to that, Eyetech, a private New York-based company with 75 employees, had raised $50 million. (See BioWorld Today, Aug. 8, 2002.)

Eyetech opened its doors more than two years ago on the idea of developing Macugen, formerly EYE001 or NX 1838, a product licensed from Foster City, Calif.-based Gilead Sciences Inc., in a $32 million deal. (See BioWorld Today, April 7, 2000.)

Macugen, likely to be injected in the diseased eye every six weeks, was developed using San Carlos, Calif.-based Inhale Therapeutic Systems Inc.'s PEGylated technology, designed to help the product stay in the system longer. (See BioWorld Today, Feb. 27, 2002.)

While Guyer wouldn't go into details, he did say Gilead would receive royalties and that Eyetech and Inhale have an "arrangement."

Meanwhile, the company has completed enrollment of its 1,200-patient Phase III pivotal studies in AMD. Guyer wouldn't discuss the projected timeline, but said, "Traditionally, in this particular field, a one-year endpoint is looked at."

In DME, Guyer said the timing of Phase III trials will depend on results of the ongoing Phase II trials.

Wet AMD, a cause of irreversible blindness, is characterized by the growth of abnormal blood vessels into the area beneath the retina. Guyer said about 15 million Americans have some form of AMD, with about 1.2 million affected by the wet form (there are approximately 200,000 new cases each year). DME affects about 135,000 Americans with diabetes each year and is the leading cause of blindness in adults under the age of 55.

QLT Inc., of British Columbia, sells a treatment for wet AMD called Visudyne (verteporfin). In September, Alcon Research Ltd., of Fort Worth, Texas, began enrolling a 500-patient Phase III study comparing its modified steroid, Anecortave Acetate, to Visudyne. (See BioWorld Today, Sept. 5, 2002.)

South San Francisco-based Genentech Inc. also is in the game, developing an antivascular endothelial growth factor antibody for AMD treatment.