BioWorld International Correspondent

Arpida Ltd. plans to move its lead compound Iclaprim into a Phase III trial in the first half of the new year, following its successful completion of a Phase II trial involving 92 patients with complicated skin and soft-tissue infections.

The Muenchenstein, Switzerland-based company is currently seeking a development partner, President and CEO Khalid Islam told BioWorld International, as well as new funding.

"We are looking to get in around €25 million relatively rapidly," he said.

At present, the company is open either to a global alliance involving a major pharmaceutical player or a regional deal in which it would retain commercialization rights for certain territories.

"This particular compound is a hospital compound, so you don't need such a large sales force," Islam said.

The Phase II trial compared safety and efficacy of two intravenous doses of Iclaprim with the current gold-standard treatment, vancomycin. The primary endpoint was clinical cure, a subjective measure based on clinicians' observations. Secondary endpoints included tolerability and microbiological response or elimination of the cause of infection.

In evaluable patients, clinical cure rates for each dose of Iclaprim were similar to that observed with vancomycin. Those receiving 1 mg/kg of Iclaprim exhibited a clinical cure rate of 92.9 percent (26 of 28 patients), as did those in receipt of standard vancomycin therapy. Patients receiving 2 mg/kg of Iclaprim exhibited a clinical cure rate of 93.5 percent (29 of 31 patients). On the secondary endpoint of microbiological response, Iclaprim performed more favorably than vancomycin. In the low-dose group, 57.1 percent (16 of 28 patients) had a complete response, while in the high-dose group, the figure was 76.7 percent (23 of 30 patients). The equivalent statistic for vancomycin was 50 percent (13 of 26 patients). The drug was well tolerated - adverse events were rare and occurred at similar frequencies across all study arms.

Iclaprim, a diaminopyrimidine, disrupts bacterial DNA synthesis by inhibiting the activity of the prokaryotic form of dihydrofolate reductase, an enzyme that catalyzes the conversion of dihydrofolate to tetrahydrofolate. The latter is an essential cofactor involved in the synthesis of all purines and the pyrimidine thymine.

The cancer drug methotrexate targets the eukaryotic enzyme, while the antibiotic trimethoprim also targets the bacterial enzyme, although it has differing pharmokinetic and microbiological profiles from Iclaprim. Trimethoprim is metabolized via the kidney, is excreted through the urinary tract and is primarily used to treat urinary tract infections in women. Iclaprim, Islam said, is metabolized via the bile duct and is passed in the feces. It is in development for treatment of infections arising from burns, ulcers, surgical abscesses, cellulites and animal bites.

Arpida licensed the compound from Basel, Switzerland-based F. Hoffman-La Roche Ltd., which will earn low-single-digit royalties on net sales, should Iclaprim undergo commercialization.

"We think that this drug will hit over $500 million, and that's a very conservative forecast," Islam said. The company aims to complete a regulatory filing in 2006 and to launch the product the following year. An oral version of Iclaprim is about six to nine months behind, Islam said, although it has not yet entered the clinic. "It's naturally orally bioavailable, so we didn't have to do that much to it," Islam said. Should it obtain approval as well, the intravenous form of the drug would remain as the front-line treatment, but the oral form could be administered as a step-down therapy, allowing earlier patient discharge from treatment centers.