BioWorld International Correspondent

Arpida Ltd. is moving its broad-spectrum injectable antibiotic iclaprim into pivotal Phase III clinical trials in patients with complicated skin and skin-structure infections, and is eyeing a new drug application filing in 2007.

The Muenchenstein, Switzerland-based company is planning to conduct two independent Phase III trials, each with several hundred subjects. "The FDA and a number of other authorities prefer to have two independent trials instead of one large trial," Arpida President and CEO Khalid Islam said. "They're trying to pave the path and simplify the process so we can get new drugs into the market."

Rising rates of methicillin resistance among Staphylococcus aureus isolates are fuelling the demand, he said.

Iclaprim, a diaminopyrimidine, acts by inhibiting the prokaryotic form of dihydrofolate reductase, an enzyme essential for bacterial DNA synthesis. The company will evaluate a 1-mg/kg dose, the lower of two doses tested in a Phase II trial. (See BioWorld International, Dec. 17, 2003.)

"The primary endpoint is clinical cure rate of iclaprim vs. the comparator," Islam said. In the Phase II study, the compound was compared to vancomycin. In the upcoming studies, which will commence toward the end of the second quarter, the comparator will be linezolid, marketed as Zyvox by Pfizer Inc., of New York. The trials will be powered to demonstrate non-inferiority to the latter product.

Iclaprim, like Zyvox, is in development for both intravenous and oral administration. An oral formulation is about to enter a Phase I trial. If it gains approval, it would enable hospitals to discharge recovering patients early and allow them to continue treatment at home. "Pfizer has already done the marketing for the intravenous to oral switch," Islam said. However, iclaprim may be competitive with Zyvox, he said, as it is bactericidal, whereas the latter is bacteriostatic.

Arpida has appointed Dennis Stevens, of the Infectious Diseases Section of the Veterans Affairs Medical Center in Boise, Idaho, as principal investigator for the U.S. leg of the Phase III program. Centers in Canada and several European countries also are participating.

The company, which originally licensed iclaprim from Basel, Switzerland-based F. Hoffmann-La Roche Ltd., has not yet partnered the compound and has yet to finalize its commercialization strategy. The company has sufficient resources to fund the clinical trial itself, having raised CHF84.3 million (US$71.5 million) in venture capital last year. "If there is a deal we cannot turn down we will definitely pick that up," Islam said. "We have the luxury to choose. We're not going to be forced into a situation."