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Recent regulatory delays for two would-be competitors in the anti-infective space have not deterred Targanta Therapeutics Corp, which submitted a new drug application as anticipated for oritavancin, a broad-spectrum antibiotic against Gram-positive bacteria.

"We're confident and excited about the" NDA for oritavancin, a semisynthetic lipoglycopeptide antibiotic that demonstrated efficacy as a short-course antibiotic therapy in two pivotal trials, said Mark Leuchtenberger, president and CEO of the Cambridge, Mass.-based firm. Targanta, he added, has been in discussions with the FDA and has been able to respond to the agency's recent changes in guidance for anti-infective therapies.

Starting in 2006, with the rejection of Louisville, Colo.-based Replidyne Inc.'s application for faropenem, the FDA began asking for more than straight-up non-inferiority data for antibiotics and, in October, strengthened the non-inferiority margins for pivotal trial protocol.

Last year, partners South San Francisco-based Theravance Inc. and Astellas Pharma US, of Deerfield, Ill., received an approvable letter for their antibiotic telavancin and, though the agency did not request additional studies, an advisory drug panel was set for Feb. 27. (See BioWorld Today, Oct. 23, 2007, and Dec. 7, 2007.)

And in December, an application by New York-based Pfizer Inc. for dalbavancin HCl, a once-weekly, two-dose antibiotic, was deemed approvable. In that case, the FDA cited the new draft guidance on anti-infectives and asked for additional dalbavancin data.

Part of the FDA's revised guidance included changing the non-inferiority margin from 15 percent to 10 percent.

The first of two Phase III studies of oritavancin was designed using a 15 percent margin; however, analyst Joel Sendek, of New York-based Lazard Capital Markets LLC, pointed out in a research note that Targanta provided the FDA with "historical data supporting the 15 percent non-inferiority study" and mentioned that other drugs, such as Tygecil (tigecycline), were approved based on that standard.

"We've been very responsive to the guidance the FDA gave in October," Leuchtenberger told BioWorld Today, and have an advantage over Pfizer and Theravance, both of which filed their applications prior to the agency's new guidance.

"We've had ample time to respond to their concerns," he said. "So we feel very comfortable in our FDA submission."

Targanta is asking for a for a six-month priority review, but even with a 10-month standard review - both Pfizer's dalbavancin and Theravance's telavancin had 10-month review periods - the company is expecting a "PDUFA date in 2008," followed by a prospective launch in 2009, said Leuchtenberger.

In addition to dalbavancin and telavancin, Targanta's drug faces a slew of others on the competitive front. Closest to market are ceftobiprole, a cephalosporin antibiotic from Basel, Switzerland-based Basilea Pharmaceutica Ltd. and a Johnson & Johnson subsidiary, and iclaprim, a diaminopyrimidine antibiotic, from Swiss firm Arpida Ltd. Ceftobiprole is under review and assigned an advisory panel meeting Feb. 28, while iclaprim is nearing a regulatory filing after achieving its primary endpoint in two pivotal trials.

Besides those in the pipeline, existing drugs vancomycin and Cubicin (daptomycin, Cubist Pharmaceuticals Inc.) are available for the particularly dangerous methicillin-resistant Staphylococcus aureus (MRSA) infections.

Targanta's oritavancin is set apart by its efficacy as a short-course treatment against Gram-positive bacteria, Leuchtenberger said. In pivotal studies, the drug demonstrated efficacy at three to seven days of treatment, compared to existing antibiotic treatment, which usually takes anywhere from seven to 14 days to clear infection.

"We believe oritavancin offers a chance to bring a paradigm shift" to the antibiotic space, Leuchtenberger said.

The short duration offers benefits to patients, he added, who are able to leave the hospital faster, thereby reducing their chances of contracting another infection. The pharmacokinetic and pharmacodynamic profile of oritavancin also shows that the drug is secreted largely unchanged through the bile, meaning that it can "sidestep the potential side effects" of other antibiotics and doesn't require dose adjustment or monitoring.

All that could lead to tremendous cost savings, Leuchtenberger added.

Originally developed by Indianapolis-based Eli Lilly & Co., which conducted the first of two pivotal trials, oritavancin later was licensed to InterMune Inc., of Brisbane, Calif., before Targanta acquired the drug in late 2005. The NDA "really is the culmination of a lot of work, starting at Lilly," Leuchtenberger said.

Targanta now plans to complete a marketing authorization application in Europe "in the months to come," he added, while finishing up a Phase II study testing a single dose of oritavancin.

Upon approval, Targanta anticipates marketing oritavancin on its own in the U.S. and taking the lead on commercialization in Europe, though it might seek distribution partners for some regions.

The company, which had $48.7 million as of Sept. 30, added $60 million in its initial public offering a month later. Leuchtenberger said Targanta should have "sufficient funds well into 2009."

Shares of Targanta (NASDAQ:TARG) rose 17 cents Monday to close at $9.