Eyetech Pharmaceuticals Inc. and partner Pfizer Inc. today are scheduled to present data supporting use of the potential blockbuster Macugen as a treatment for neovascular or wet age-related macular degeneration.
The partners will go before the Dermatologic and Ophthalmic Drugs Advisory Committee, which has been asked to decide, among other things, whether the trial data are sufficient and if the benefits of using Macugen outweigh the risks. The FDA is not bound by the panel's recommendations.
Already the agency awarded the New York-based firms priority-review status on the rolling new drug application filed June 17 under fast-track status. The NDA also was entered into the Pilot 1 program, which allows the FDA to complete reviews of individual reviewable units within six months of submission and provide early feedback on the pre-submissions. (See BioWorld Today, June 18, 2004.)
Meanwhile, an FDA briefing document released Thursday on the NDA did not contain a recommendation for the drug.
Albert Rauch, vice president at A.G. Edwards in St. Louis, told BioWorld Today he expects the panel to ask for more data for full approval, but "because of the seriousness of the indication, they will probably get an accelerated approval."
Macugen (pegaptanib sodium injection) is a pegylated anti-VEGF aptamer, which binds to and thus inhibits the activity of vascular endothelial growth factor (VEGF). VEGF is a protein that plays a critical role in angiogenesis and increased leakage from blood vessels, two of the primary pathological processes responsible for the vision loss associated with neovascular age-related macular degeneration (AMD).
The NDA is based on two prospective, multicenter, randomized, double-masked controlled trials in which intravitreous injections of Macugen (0.3 mg, 1 mg or 3 mg) were administered every six weeks for 48 weeks with a follow-up period of 54 weeks, totaling a maximum of nine injections. Study EOP1003 included 622 patients and study EOP1004 included 586 patients.
The primary efficacy endpoint was the portion of responders, defined as patients avoiding 15-letter loss of visual acuity, a clinically meaningful benefit for a patient.
According to the analysis, the 0.3-mg dose achieved statistical significance for a clinically meaningful primary efficacy endpoint in the two trials.
Macugen 1 mg also achieved a statistically significant treatment benefit in study EOP1003 and was near significance in EOP1004.
"Dose levels of 1 mg and 3 mg were effective in combined analyses but did not exhibit additional benefit over that seen at the 0.3-mg dose levels," the companies said.
Indeed, Rauch said the question is whether the 0.3-mg dose level is optimal.
"It does look like [Macugen] overall is efficacious, but I think dose-response curves give people sort of a good feeling in that you've got the optimized dose," he said. "Or, maybe a lower dose would be better."
He added that it looks like 0.3 mg works best in minimally classic macular degeneration, while results for predominately classic and occult were mixed. (AMD cases include three subtypes - predominantly classic, minimally classic and occult.)
While Rauch doesn't believe there are major safety problems with Macugen, he did say there appears to be a concern related to the intravitreous injection procedure that must be done every six weeks.
"But, the trials didn't control for that, so you don't know if the side effects are due to the needle going in, because they inject the placebo patients," he said.
Whatever the case, Rauch believes Macugen is an important drug. Whether it will be a blockbuster - like so many analysts believe - is another question.
Rauch said Macugen will, at the very least, pull in what Vancouver, British Columbia-based QLT Inc.'s Visudyne makes. Approved in 2000 to treat the predominately classic form of wet AMD, Visudyne sales in 2003 were $357 million. Sales for the first two quarters of 2004 totaled about $210 million. 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.
Noting the potential of Macugen, Pfizer in late 2002 signed on as Eyetech's partner in a deal potentially worth $750 million (including a $100 million up-front fee) for Eyetech. The two will co-market Macugen in the U.S. and share profits. Pfizer has exclusive rights to develop and commercialize Macugen overseas. (See BioWorld Today, Dec. 19, 2002.)
FDA acceptance of the new drug application Aug. 17 triggered a $10 million milestone for Eyetech.
Meanwhile, Eyetech has performed well on its own this year, raising $136.5 million in its initial public offering Feb. 1. The stock priced at $21 per share and rose to $32.40 by the end of its first day. (See BioWorld Today, Feb. 2, 2004.)
Thursday, Eyetech's stock (NASDAQ:EYET) was up $3.92, or 11.1 percent, to close at $39.20.
For the quarter ended June 30, Eyetech reported $253.2 million in cash, cash equities and marketable securities.
Development of Macugen continues in retinal vein occlusion and diabetic macular edema, for which the product also has FDA fast-track designation. Eyetech licensed Macugen from the Selex technology portfolio developed by Gilead Sciences Inc., of Foster City, Calif., in 2000.