Macugen well-received by advisory panel; points of concern remain

ROCKVILLE, Md. — A drug being developed for the treatment of wet age-related macular degeneration seems to slow vision loss but does not significantly improve vision, according to testimony before an advisory panel to the Food and Drug Administration on Friday.

The FDA panel reviewed studies by Pfizer and Eyetech assessing the safety and efficacy of Macugen (pegaptanib sodium injection).

The advisory panel did not formally vote on whether Macugen should be approved. The FDA presented the panel with questions regarding the data, and it will consider the panel’s opinions as the agency moves forward in its expedited approval process for the drug.

“The FDA had a clinical submission from Eyetech. … We did not think it was beneficial to vote, so we simply asked questions to help review the data,” said Wiley Chambers, MD, deputy director of the Ophthalmic Division of Anti-Inflammatory, Analgesic and Ophthalmic Drug Products for the FDA, briefing reporters after the meting. He said the meeting had no impact on how soon the drug would be approved.

Dr. Chambers said the Macugen data submission is part of a “rolling” application, an FDA pilot program that allows companies to submit an application in several parts as it becomes available. The process is designed to speed drug approval times, he said.

The data under consideration included 54-week follow-up. Eyetech has said it will submit additional information once 2-year data is available.

David Guyer, MD, chief executive officer of Eyetech, and Anthony Adamis, MD, the company’s chief scientific officer and vice president of research, presented data on 0.3 mg, 1 mg and 3 mg dosing regimens of Macugen. Total enrollment in the trial was 1,186 patients, randomized to Macugen or a sham injection. The drug slowed the progression of vision loss at all three dosing levels. Patients receiving the 0.3 mg dose every 6 weeks had 15% less vision loss than patients receiving placebo. At 54 weeks, 70% of patients given the lowest dose lost fewer than three lines of Snellen acuity, compared with 55% of patients receiving placebo.

Of concern to panel members were 12 cases of endophthalmitis reported among the Macugen users. Eyetech responded that last year researchers began preparing the injection site with povidone iodine, which they said appeared to have prevented further cases of infection.

Panel members also questioned the validity of visual acuity testing conducted at 2 m rather than the standard 4 m; Eyetech responded it had “taken precautions” to avoid variations.

The panel also addressed potential cardiovascular concerns in association with Macugen. Macugen works by inhibiting a protein needed in blood-vessel formation, according to Eyetech. The FDA recently mandated the manufacturer of another VEGF inhibitor approved for colon cancer to warn physicians that patients on the drug have a higher chance of developing blood clots.