While Oscient Pharmaceuticals Corp. missed its primary endpoint in a Phase II trial of Ramoplanin for the treatment of Clostridium difficile-associated diarrhea, the firm believes the trial's preliminary data are encouraging, and hopes to move into Phase III studies by the end of the year.
Ramoplanin is a novel antibiotic being studied by Waltham, Mass.-based Oscient as a treatment for hospital-acquired C. difficile-associated diarrhea, or CDAD, and for the prevention of bloodstream infections caused by vancomycin-resistant enterococci.
The candidate, licensed by Oscient (formerly Genome Therapeutics Corp.) from King of Prussia, Pa.-based Vicuron Pharmaceuticals Inc., has been granted FDA fast-track status.
The 87-patient Phase II trial reported on after the market closed Tuesday was a three-arm, open-label, non-inferiority study comparing Ramoplanin 200 mg twice daily (n=28), Ramoplanin 400 mg twice daily (n=29) and vancomycin 125 mg four times daily (n=29) to treat CDAD.
According to the company, the response rates at the test-of-cure visit (7-14 days post-therapy), the primary endpoint of the trial, were 71 percent in the Ramoplanin 400-mg arm and 78 percent in the vancomycin arm. Although response rates for those two arms were comparable, non-inferiority was not statistically demonstrated because the observed response rates of all arms, including the vancomycin arm, were lower than the previously published vancomycin response rates.
Steven Rauscher, president and CEO of Oscient, told BioWorld Today the study was powered to reach non-inferiority based on the expected response rate in the literature for vancomycin, which was 95 percent. "Some of those literature references are from the 1980s or before, so it looks like the overall response rate for vancomycin is lower than it used to be," he said. "So for that statistical reason, we cannot say the study achieved its endpoints."
Vancomycin was the comparator drug because it is the only FDA-approved product for treating CDAD, Rauscher said.
There was a dose-response relationship in the Ramoplanin arms, with a higher response rate seen with the 400-mg dose. Additionally, Ramoplanin 400 mg and vancomycin had response rates at end of therapy (a secondary endpoint) of 85.2 percent and 85.7 percent, respectively, the company said.
Rauscher said the company will discuss the data with the FDA and decide how to proceed.
"We are pretty comfortable ourselves, but we do need to do some further analysis," he said, adding that if the firm uses vancomycin as its test agent in the Phase III program, the assumed response rate will be modified.
Meanwhile, in the past month, the company closed enrollment in the Phase III trial of Ramoplanin in vancomycin-resistant enterococci once the trial had two-thirds of its 950 originally scheduled patients. (The Phase III was under way when Oscient acquired the candidate from Vicuron in late 2001.)
Even though Oscient continued enrollment after the acquisition, the firm began placing more emphasis on CDAD, believing it would be the first approved indication.
In other news this week, the company said the August issue of Respiratory Medicine will include reports of two new studies evaluating the efficacy and safety of Factive (gemifloxacin mesylate) tablets for the treatment of community-acquired pneumonia (CAP) and acute bacterial exacerbations of chronic bronchitis (ABECB).
The studies compared Factive tablets to two commonly used antibiotics and measured clinical and bacteriological response at various time points post-therapy.
Factive is a broad-spectrum member of the fluoroquinolone class approved by the FDA for the treatment of CAP (of mild to moderate severity) and ABECB. Tablets currently are being introduced to health care providers.
Oscient also is developing an intravenous formulation of Factive for use in hospitalized patients.
Factive was discovered by Korea-based LG Life Sciences and later licensed to South San Francisco-based Genesoft Pharmaceuticals Inc., the firm that merged with Genome Therapeutics to create Oscient. (See BioWorld Today, Feb. 10, 2004.)
Oscient's stock (NASDAQ:OSCI) fell 22 cents Wednesday to close at $3.63.