Theravance goes for three with Telavancin in Staphylococcus aureus

Phase 3 trial designed to support regulatory filing; potential to expand label for VIBATIV (telavancin) to third difficult-to-treat, gram-positive infection type

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GEORGE TOWN, Grand Cayman—Theravance Biopharma, Inc. today announced enrollment of the first patient in the company’s Phase 3 registrational study of telavancin in patients with Staphylococcus aureus bacteremia. The trial is designed to support a regulatory filing for telavancin as a treatment for Staphylococcus aureus bacteremia.  Bacteremia is the presence of bacteria in the bloodstream and represents a significant unmet medical need. There are only two currently approved antibiotics for the treatment of this infection and treatment failure is common in these patients, particularly when the infection is methicillin-resistant Staphylococcus aureus (MRSA).
Theravance Biopharma markets telavancin in the U.S. as VIBATIV in the product’s two currently approved indications. These include the treatment of adult patients with hospital-acquired and ventilator-associated bacterial pneumonia (HABP/VABP) when alternative treatments are not suitable and in complicated skin and skin structure infections (cSSSI) caused by susceptible isolates of gram-positive bacteria, including Staphylococcus aureus, both methicillin-susceptible (MSSA) and methicillin-resistant (MRSA) strains.
VIBATIV is a bactericidal, once-daily, injectable lipoglycopeptide antibiotic with in-vitro potency and a dual mechanism of action whereby telavancin both inhibits bacterial cell-wall synthesis and disrupts bacterial cell-membrane function. The drug’s proven efficacy against difficult-to-treat infections has been demonstrated in several large, multinational registrational studies, which involved one of the largest cohorts of patients with MRSA infections studied to date.  Recently presented study analyses at key scientific conferences further supplement the extensive and well-documented evidence of the drug’s in-vitro potency and in-vitro activity against a broad collection of bacterial pathogens, including those that are considered difficult-to-treat and multidrug-resistant.
“Bacteremia is a serious healthcare system challenge associated with significant morbidity and mortality and is in need of new, effective antibiotic treatments,” stated Rick E Winningham, chairman and CEO. “We have previously seen evidence of the potential for telavancin to successfully treat gram-positive bloodstream infections in our Phase 2 uncomplicated Staphylococcus aureus bacteremia study, as well as investigator-initiated studies. Based on these promising signs of activity for telavancin, and the acute healthcare system need for effective antibiotics for these difficult to treat infections, we have decided to conduct this registrational Phase 3 study.” 
The Phase 3 trial is a multi-center, randomized, open-label study that will enroll approximately 250 adult patients with confirmed methicillin-sensitive Staphylococcus aureus (MSSA) or MRSA bacteremia at about 70 clinical sites in the U.S. and around the world. Researchers will evaluate the non-inferiority of telavancin in treating these patients as compared to standard therapies such as vancomycin, daptomycin and anti-staphylococcal penicillins.
“Mortality rates for MRSA bacteremia range up to 30 percent despite currently available treatments,” stated G. Ralph Corey, M.D., professor of medicine at Duke University School of Medicine and a principal investigator for the bacteremia trial. “The most difficult-to-treat cases of Staphylococcus aureus bacteremia need new options as treatment failures commonly occur in these patients.  Based on the profile of VIBATIV, we are interested in evaluating whether this antibiotic can help increase the number of patients who have positive clinical outcomes.”
Theravance Biopharma believes that VIBATIV has the potential to be an effective treatment for Staphylococcus aureus bacteremia based on several key product attributes:
VIBATIV has demonstrated potent in-vitro bactericidal activity against Gram-positive bacteria such as Staphylococcus aureus, including MRSA. Staphylococcus aureus is a leading cause of bacteremia.
The efficacy of VIBATIV is evidenced by the clinical cure rates demonstrated in its large, pivotal, multi-center, multinational, double-blind, randomized Phase 3 clinical trials in patients with complicated skin and skin structure infections (cSSSI) and hospital-acquired and ventilator-associated bacterial pneumonia (HABP/VABP).
VIBATIV possesses a dual mechanism of action with which it kills bacteria by both inhibiting cell wall biosynthesis and disrupting membrane barrier function.
VIBATIV has demonstrated significant penetration into important lung and tissue sites including pulmonary epithelial lining fluid, alveolar macrophages and skin blister fluid.
“We believe that there is a compelling rationale supporting the potential of VIBATIV as an antibiotic treatment for Staphylococcus aureus bacteremia, particularly those difficult to treat infections caused by MRSA,” said Winningham. “If we are successful with this Phase 3 study and a subsequent regulatory filing, VIBATIV will be the only branded antibiotic to be approved in bacteremia, HABP/VABP and cSSSI—three difficult to treat, gram-positive infections.”
Bacteremia represents a serious medical condition that can lead to the spread of infection throughout the body, as well as the potentially fatal conditions of sepsis and septic shock. Staphylococcus aureus is a leading cause of bacteremia and treatment failure is fairly common, particularly when the infection is caused by MRSA.  Mortality rates associated with Staphylococcus aureus bacteremia remain high, reported in the range of 20-30 percent. Mortality is higher among patients with MRSA infection.
VIBATIV was discovered internally in a research program dedicated to finding new antibiotics for serious infections due to Staph and other gram-positive bacteria, including MRSA. Theravance Biopharma plans to market VIBATIV in markets outside the United States where the drug is approved through a network of partners. In Europe, VIBATIV is indicated for the treatment of adults with nosocomial pneumonia including ventilator associated pneumonia, known or suspected to be caused by MRSA. VIBATIV should be used only in situations where it is known or suspected that other alternatives are not suitable. VIBATIV is not currently indicated for the treatment of cSSSI in Europe.
Clinigen Group holds the commercial rights to market and distribute VIBATIV in Europe. Theravance Biopharma also has partners in the following geographies—Canada, Middle East, North Africa, Israel, and Russia. Discussions continue regarding potential partnering relationships in other parts of the world.

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