Washington Editor

Oscient Pharmaceuticals Corp. received the FDA's blessing through a special protocol assessment that sets a clear path toward Ramoplanin's approval for Clostridium difficile-associated disease, and though it took about a year to settle on the arrangement, President and CEO Steven Rauscher said it was necessary to establish an appropriate approach.

"It was challenging because there has not been a new antibiotic approved for the treatment of C. difficile in 30 years," he told BioWorld Today. "So there really was not a well-characterized regulatory terrain for this. It was important for us, before we embarked on a Phase III program, to make sure that we had consensus with the FDA on exactly how to measure patient results."

Per terms of the regulatory agreement, which Rauscher called "a pretty important step" for the Waltham, Mass.-based company, the program will include a pair of Phase III trials running concurrently to measure response rate at end of therapy as their primary endpoint. That quantitative measure will factor in metrics such as abdominal pain, fever and stool symptoms. The trials are powered to 90 percent and assume a 70 percent response rate.

If completed successfully, the studies would support approval of the bactericidal agent against C. difficile, a bacterium that causes diarrhea and colitis.

Designed as double-blinded, non-inferiority studies, they each will enroll about 490 patients in the U.S., Canada and other parts of the world and randomize them to receive either Ramoplanin 200 mg twice daily or four 125-mg doses of vancomycin per day for 10 days. That comparator antibiotic is the only drug with FDA approval in that indication.

The pivotal program's design is based largely on findings from a Phase II trial in the indication's previously more restrictive appellation, C. difficile-associated diarrhea. That study showed an 85.2 percent response rate among patients receiving 400 mg of Ramoplanin compared to 85.7 percent for those on vancomycin. But that study was a miss, as the non-inferiority endpoint was not reached a week to two after therapy, when there was a 71 percent response rate for the 400-mg Ramoplanin group and 78 percent for the vancomycin group. The trial also tested a 200-mg dose of Ramoplanin, which ended up as the dose selected for Phase III. (See BioWorld Today, Aug. 12, 2004.)

Rauscher said Ramoplanin primarily differs from vancomycin in terms of its mechanism of action, as the former acts at a different point of the cell wall, and there is no cross resistance between Ramoplanin and the glycopeptide family of antibiotics, to which vancomycin belongs. Also, because injectable vancomycin's extensive use in hospitals for systemic Staph infections leads to a reluctance to prescribing it for C. difficile, Ramoplanin might be viewed as "vancomycin-preserving," as it would only be used as a gastrointestinal antibiotic.

He added that while the two products exhibit comparable in vitro potency, Ramoplanin's dosing schedule is more favorable.

Rauscher declined to specify when the new studies would begin or comment on their duration. Those details will come after additional discussions with partner Pfizer Inc., the New York-based pharmaceutical firm that recently paid $1.9 billion to acquire the antibiotic company Vicuron Pharmaceuticals Inc., of King of Prussia, Pa.

Oscient originally licensed the product's North American rights four years ago from Milan, Italy-based Biosearch Italia SpA. Per that initial agreement, Pfizer is responsible for providing bulk supplies of the drug for Phase III and commercialization, and Oscient funds all clinical work with its own resources. In return, Pfizer has access to all Oscient-generated data for its regulatory plans elsewhere in the world.

An earlier Phase III program for Ramoplanin, began by Biosearch, tested the product in vancomycin-resistant enterococci bloodstream infections. But eventually Oscient came to view the indication as secondary and stopped a slow-enrolling Phase III study to focus resources on C. difficile.

Those infections have been a concern for patients who have had recent antibiotic therapy and/or hospital stays, resulting in about 400,000 to 500,000 cases per year in the U.S. Its incidence and severity are on the rise, and in some cases there has been no antibiotic therapy or exposure to hospitals in patients. It is treated with vancomycin and metronidazole, and Rauscher estimated that up to half of oral vancomycin prescribed for C. difficile is used outside hospitals and in community settings. Since such prescriptions are often tied to primary care physicians, Oscient has lined up a good fit with its existing 300-person sales force that markets oral tablets called Factive (gemifloxacin mesylate) for bronchitis and pneumonia to those primary care providers.

Going forward, the company is developing an intravenous formulation of Factive for use in hospitalized patients. It also promotes Testim 1 percent testosterone gel, a product from Auxilium Pharmaceuticals Inc., of Norristown, Pa.

On Wednesday, Oscient's stock (NASDAQ:OSCI) gained 17 cents to close at $2.35.