Theravance Inc. and partner Astellas Pharma US Inc. said the FDA issued an approvable letter for telavancin, a once-daily, injectable antibiotic, in complicated skin and skin structure infections caused by Gram-positive bacteria, including the increasingly prevalent methicillin-resistant Staphylococcus aureus (MRSA) strain.

South San Francisco-based Theravance said it plans to meet with the agency to resolve outstanding issues, though CEO Rick Winningham assured investors during a conference call that "no additional clinical studies need to be initiated" to provide a complete response to the approvable letter. Those issues include resolving the manufacturing compliance issues of a third-party manufacturer, which Winningham stressed were not specifically related to telavancin, as well as three potential options with regard to the data.

Theravance and Astellas can submit "either a revised label or a reanalysis of the data or additional data," Winningham said, though he declined to disclose exactly what any of those efforts would entail.

Company executives, however, have maintained since the filing of telavancin's new drug application late last year that the drug would not likely be foiled by the FDA's shift in requiring more than just proof of noninferiority for antibiotic approvals.

According to Theravance, data from two pivotal studies, both of which demonstrated telavancin's noninferiority to vancomycin, in cSSSI also showed a level of noninferiority in both studies that exceeded 20 percent in most measures. (See BioWorld Today, Dec. 11, 1006.)

Despite attempts by several analysts on the call to discern the FDA's precise language in the approvable letter, Theravance's management team remained mum on the specifics, stating only that the agency's concerns were straightforward and would be addressed as quickly as possible. "We're in ongoing communications" with the FDA, Winningham said, "and it would be inappropriate for us to comment" further.

They remained equally cryptic on the manufacturing snag. Winningham said Theravance is working with a "reputable" U.S.-based sterile products supplier that was called out by the agency regarding undisclosed quality and laboratory issues, but that "we would expect them to resolve [those] in a rapid manner."

News of the approvable letter didn't have much effect on the company's stock (NASDAQ:THRX), which closed at $24.80 Monday, down 66 cents.

Telavancin's approvable letter comes amid recent stories of MRSA-related deaths and follows a federal report issued earlier this month showing that MRSA caused more than 94,000 life-threatening infections and nearly 19,000 deaths in the U.S. in 2005.

The drug also falls squarely in the pack of potential alternative therapies for skin infections caused by the resistant pathogen. To date, only a few options, such as vancomycin and Cubicin (daptomycin, Cubist Pharmaceuticals Inc.) are available for MRSA patients, though there are several in development that are nearing the finish line. Besides telavancin, cephalosporin antibiotic ceftobiprole and dalbavancin, a semisynthetic glycopeptides, both are under FDA review in cSSSI. Ceftobiprole is being developed by Basel, Switzerland-based Basilea Pharmaceutica Ltd. in partnership with New Brunswick, N.J.-based Johnson & Johnson, and dalbavancin belongs to New York-based Pfizer Inc.

Swiss firm Arpida Ltd. is approaching regulatory filing with iclaprim, a diaminopyrimidine antibiotic, which achieved its primary endpoint in two pivotal trials. That new drug application is expected later this year. Targanta Therapeutics, of Cambridge, Mass., is in late-stage trials with oritavancin, a glycopeptides antibiotic, and anticipates submitting an NDA in the first part of 2008, while ceftaroline acetate, which New York-based Forest Laboratories Inc. acquired in its January buyout of Cerexa Inc., is set to start Phase III trials in cSSSI.

Telavancin, which is partnered with Deerfield, Ill.-based Astellas in a potential $235 million worldwide collaboration, also is being tested in a Phase III trial in hospital-acquired pneumonia. Pending positive results, the partners intend to submit a separate NDA in that indication.

Elsewhere in its pipeline, Theravance aims to advance TD-1792, a Phase II-stage antibiotic, which Astellas opted in September not to license for further development. It also plans to move forward on TD-5108, a 5-HT4 agonist that completed Phase II testing in chronic constipation. London-based GlaxoSmithKline plc passed on that program, also in September, though Theravance told investors that the compound had yielded positive data to date. (See BioWorld Today, Sept. 10, 2007.)

The company intends to provide updated financial guidance during its third-quarter earnings call later this week, though Chief Financial Officer Michael Aguiar said that Theravance is "really in a good position," with multiple options for boosting its balance sheet, including equity or debt financings or finding new partners for TD-1792 and TD-5108.

The firm, which reported a net loss of $45.1 million, or 75 cents per share, for the second quarter, had a total of $150.6 million in cash, cash equivalents and marketable securities as of June 30, 2007.