Washington Editor

Theravance Inc. began enrolling patients in another Phase III study of its lead investigational antibiotic, telavancin.

Called ATTAIN (Assessment of Telavancin for Treatment of MRSA Pneumonia), the multinational, multicenter, double-blinded study is designed to assess telavancin's efficacy and safety compared to vancomycin in treating hospital-acquired pneumonia caused by Gram-positive organisms such as Staphylococcus aureus and Streptococcus pneumoniae. Telavancin last month entered a Phase III study for complicated skin and skin-structure infections.

"Because we have a lot of confidence in the compound's ability to treat these serious infections," said David Brinkley, Theravance's senior vice president of commercial development, "we've designed our Phase III trials to be different than those of other products that are on the market or coming to market."

He told BioWorld Today that the new study is designed with two primary clinical cure endpoints vs. the vancomycin arm: a standard endpoint of non-inferiority overall, and a superiority endpoint of clinical cure among those patients with methicillin-resistant S. aureus (MRSA) infections. Brinkley noted that non-inferiority to standard of care is required for FDA approval, and the South San Francisco-based company expects the latest study to prove telavancin's ability to cure MRSA patients, as well.

In fact, both Phase III trials are powered to evaluate the drug's abilities in the face of MRSA. Running in parallel, the studies will include 1,500 patients apiece, and the company expects to enroll 500 MRSA patients in each.

"We are hopeful and optimistic," Brinkley said, "that we are going to be able to hit that co-primary endpoint based on results that we've seen in Phase II, Phase I, in vivo and in vitro work."

Telavancin's antibacterial activity results from interaction with D-Ala-D-Ala-containing peptidoglycan intermediates that leads, at submicromolar concentrations, to the inhibition of the transglycosylation step of peptidoglycan synthesis during cell wall synthesis. Also, at higher concentrations, direct effects on bacterial membrane function, such as dissipation of membrane and increased permeability, are observed.

"It's a lipoglycopeptide, which is a fairly new class of antibiotics," Brinkley said. "While it works the way that vancomycin works, the inhibition of peptidoglycan synthesis, it also has an additional mechanism of action that can affect membrane permeability and cell structure. We believe that this novel mechanism of action is one thing that contributes to its rapidly bactericidal activity, unlike vancomycin, which is bacteriostatic."

He declined to provide a timeline for finishing the two Phase III programs, and also did not disclose whether the company plans to test the injectable antibiotic in other infections. Looking down the road, the company has yet to determine whether to submit a new drug application based on both programs or file separate submissions. Further in the future, Theravance expects to seek a co-promotion partner in the U.S. and find commercial partners for overseas territories.

The company discovered telavancin by applying multivalent drug design in a research program dedicated to finding new antibiotics for serious infections due to S. aureus, including multidrug resistant strains and other Gram-positive pathogens.

In addition to its telavancin program, Theravance has another late-stage program, its Beyond Advair collaboration with GlaxoSmithKline plc, of London. That program has moved beyond Phase IIa studies. Theravance, which last fall priced a $98.4 million initial public offering, also is involved in a broader partnership with GSK in which the latter has an option to the former's other portfolio products. Those options include access to programs across a number of therapeutic areas including respiratory disease, overactive bladder and gastrointestinal disorders.

In exchange, Theravance received up-front funding and sold about 19 percent of its stock to GSK.

On Thursday, Theravance's shares (NASDAQ:THRX) gained 27 cents to close at $17.27.

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