Washington Editor

The FDA on Monday publicized side-effect concerns around Factive (gemifloxacin mesylate), Oscient Pharmaceuticals Corp.'s drug that is being reviewed by an advisory committee today.

The anti-infective already is approved for acute bacterial exacerbations of chronic bronchitis and community-acquired pneumonia (CAP) over a seven-day treatment course. Waltham, Mass.-based Oscient has applied for a broader label to treat both acute bacterial sinusitis and CAP over five days.

The FDA is scheduled to act on the supplemental new drug application for CAP by Sept. 21, but this gathering of the Anti-Infective Drugs Advisory Committee is solely related to the sinusitis submission.

Reviewers at the FDA are worried about Factive's association with serious skin rashes in treating sinusitis. There were 24 cases found in a recent analysis of the Adverse Event Reporting System, including serious allergic reactions and others requiring hospital treatment. They suspect that some of those cases might be Stevens-Johnson syndrome, a particularly serious rash, although no such definitive diagnoses were made.

In its briefing document to its advisory committee members, the agency concluded that the company has not demonstrated that Factive's benefit in sinusitis outweighs the "disproportionately higher risk of rash" and concern regarding severe cutaneous reactions that may occur in those patients.

Company representatives could not be reached for comment, but the supplemental new drug application for sinusitis includes data from five Phase III trials involving more than 1,800 patients who received Factive, 1,100 of whom took the drug for five days. In those trials, conducted by Factive's former owner, London-based GlaxoSmithKline plc, a 320-mg daily dose produced high clinical and bacteriologic response rates and met all predefined endpoints for non-inferiority.

In addition, the filing included a proposal for a post-approval epidemiological study to address safety concerns, but the FDA recommended that this study be completed prior to approval for sinusitis. When Oscient rejected that suggestion, the FDA first refused to accept the submission but eventually accepted it under protest.

The agency's briefing document suggested that any benefit Factive provides to sinusitis sufferers should be more clearly defined to weigh the magnitude of the product's risks. In its text, the FDA noted that its recommendations regarding Factive use for sinusitis "have been consistent across several submissions for this indication," and there remains concern that the incidence of skin reactions "is greater than comparator therapy" based on clinical trial findings and post-approval data.

According to Oscient's website, drug-related rash was reported in 2.8 percent of Factive patients in one trial of five-day sinusitis treatment and was more commonly observed in those younger than 40, especially females. In addition, the rate of rash increased with treatment longer than the maximum-labeled duration of 7 days.

Despite the FDA's negativity, Oscient's stock (NASDAQ:OSCI) gained 5 cents on Monday to close at $1.14.

A broader Factive label clearly could boost sales, said Hamed Khorsand, a senior research analyst with BWS Financial in Los Angeles. He said an expanded label encompassing the sinusitis and five-day CAP indications would add between $100 million and $150 million in revenue over the next five years. The product produced $2.6 million in sales in the last quarter and $11.9 million over the first six months of this year, reflecting its heavier seasonal use in the cooler months.

Khorsand said the rash frequency is "not a big deal," but he expressed concern over Oscient's protest to secure the meeting. His firm assigned no value to the advisory committee meeting, he said, adding that if it produces a negative outcome, the stock might see a reversal in today's gains, if that much. "I don't think the market should put any value on this meeting" until the outcome is known, Khorsand said.

He noted that the FDA's coming decision on the five-day CAP application, about which he's optimistic, represents a stronger catalyst for the stock.

Absent any new indications, Khorsand forecasted Factive sales of $100 million next year, well ahead of this year's probable $40 million to $45 million this year, as physicians become more and more comfortable with prescribing it. Oscient employs a 200-person sales force to market the drug.

The FDA is scheduled to complete its review for sinusitis by Dec. 15.