Washington Editor

GAITHERSBURG, Md. - The FDA's Anti-Infective Drugs Advisory Committee voted against expanding the label for Factive (gemifloxacin) to include acute bacterial sinusitis, absent an additional study to demonstrate its superiority.

The antibiotic's owner, Oscient Pharmaceuticals Corp., applied last year to market it as a five-day treatment for the condition, but regulators have questioned whether Factive's treatment benefits offset its risks given existing data on the drug. Executives from the Waltham, Mass.-based company declined to comment following the decision or detail what the next steps could entail.

But the FDA's position was clear.

"A superiority study would be very helpful in establishing [Factive's] benefit," said Acting Chairman John Edwards, of UCLA, echoing agency reviewers and representatives from two consumer groups who said such trials would better establish the effectiveness of any product in the indication going forward. That signals a further shift away from noninferiority studies in this setting, reflecting the FDA's continuing movement in that direction despite a lack of formal guidelines.

"We just don't have the data," said Carol Kauffman, of the Veterans Affairs Health care System. She concurred with the majority in an 11-2 vote against Factive, and every committee member in that camp said there needs to be another study. Almost all of them said they would expect it to succeed.

"For approval of the product," said the FDA's Renata Albrecht, "we need to have substantial evidence" of both efficacy and safety. She and others at the agency highlighted several concerns about Factive that led them to conclude that it has an unsuitable risk-benefit profile in the indication, most notably its link to cutaneous skin reactions such as rashes. Worries related to Stevens-Johnson syndrome, a sometimes fatal rash, also were noted.

Those risks, they said, are not outweighed by treatment benefits with the product, although company speakers countered that rashes occur in only about 2.6 percent of Factive-treated patients and primarily were mild to moderate in nature. Women younger than 40 are most prone to rashes during Factive treatment.

The FDA questioned the company's efficacy claims, which were based on results from multiple non-inferiority trials. The supplemental new drug application for sinusitis includes data from five Phase III trials that were conducted by Factive's former owner, London-based GlaxoSmithKline plc.

FDA reviewers also said that patients who have an allergic reaction to the fluoroquinolone drug would be excluded from future treatment with the entire quinolone class, eliminating an important antibiotic option.

In contrast, Oscient Director Gary Patou said that Factive would add to physicians' antibiotic arsenals and also noted that the product would be a good option in patients who have failed previous antibiotic treatments. Several committee members shared that same sentiment on second-line use. The University of Pittsburgh's Berrylin Ferguson, who spoke on behalf of Oscient, said physicians need "more effective antibiotics" for treating acute bacterial sinusitis.

Factive already is approved as a five-day treatment for acute bacterial exacerbations of chronic bronchitis and community-acquired pneumonia (CAP) over a seven-day treatment course. A drug with heavier seasonal use in the cooler months, it has generated $11.9 million in sales over the first six months of this year.

Aside from rashes, its safety profile rated well with the advisory committee members. They generally were split on the product's efficacy in treating acute bacterial sinusitis, absent any risk considerations. With a nod toward safety, though, Duke University's Richard Frothingham suggested that Factive's existing label should better emphasize the rash issue. He also suggested that product sampling should be suspended.

The agency has until Dec. 15 to make a decision on Factive's use in acute bacterial sinusitis. If approved, the product would join the other 20 options physicians have to treat acute bacterial sinusitis. The company also is seeking to sell the product for CAP over five days, and the FDA is scheduled to act on that supplemental new drug application by Sept. 21. Patou suggested that the company plans to shift its entire Factive franchise to five-day use for all indications, and risks would be minimized by packaging the product in fixed-dose prescriptions.

A broader label would significantly expand Factive's sales potential, analysts have said. Oscient's stock (NASDAQ:OSCI) was halted Tuesday, but closed at $1.14 Monday.