Theravance, Inc. (NASDAQ: THRX) and Astellas Pharma US, Inc. announced today that the U.S. Food and Drug Administration (FDA) has approved VIBATIV™ (telavancin) for the treatment of adult patients with complicated skin and skin structure infections (cSSSI) caused by susceptible Gram-positive bacteria, including Staphylococcus aureus, both methicillin-resistant (MRSA) and methicillin-susceptible (MSSA) strains. VIBATIV is a bactericidal, once-daily injectable lipoglycopeptide antibiotic discovered by Theravance.

"We are very pleased with the FDA's approval of VIBATIV, and extremely excited about the prospect of bringing this new medicine to the market," said Rick E Winningham, Theravance's Chief Executive Officer. "This is a significant event that marks the first approved indication for VIBATIV and validates Theravance's strategies in drug discovery and development. We believe that VIBATIV will become an important medicine addressing the urgent medical need for new antibiotics to treat Gram-positive infections caused by MRSA."

"VIBATIV has demonstrated its efficacy and safety in clinical trials for the treatment of Gram-positive complicated skin and skin structure infections which included the largest cohort of patients with methicillin-resistant Staphylococcus aureus studied to date," said Ralph Corey, M.D., Professor of Medicine at the Duke University Medical Center and the principal investigator in the ATLAS program. "I believe VIBATIV will be a welcome addition for physicians treating this serious infection."

"VIBATIV will provide physicians with a new option to help their patients and demonstrates our long-standing commitment to the anti-infective community," said Seigo Kashii, President and Chief Executive Officer at Astellas Pharma US, Inc. "This approval milestone is a good example of Astellas' strong focus on improving the health of patients around the world through innovative medications."

VIBATIV will be marketed and sold by Astellas and is expected to be commercially available in the United States during the fourth quarter of 2009. Theravance will collaborate with Astellas in marketing in the United States for the first three years following approval.

About VIBATIV

VIBATIV was discovered by Theravance in a research program dedicated to finding new antibiotics for serious infections due to Staphylococcus aureus and other Gram-positive bacteria, including MRSA. VIBATIV is a bactericidal, once-daily, injectable lipoglycopeptide antibiotic with a dual mechanism of action whereby VIBATIV both inhibits bacterial cell wall synthesis and disrupts bacterial cell membrane function. VIBATIV is indicated for the treatment of adult patients with cSSSI caused by susceptible isolates of the following Gram-positive microorganisms: Staphylococcus aureus (including methicillin-susceptible and -resistant isolates), Streptococcus pyogenes, Streptococcus agalactiae, Streptococcus anginosus group (includes S. anginosus, S. intermedius and S. constellatus) and Enterococcus faecalis (vancomycin-susceptible isolates only).

About ATLAS I and ATLAS II Clinical Studies

The VIBATIV Phase III clinical program consisted of two large, multinational, double-blind, randomized Phase III clinical studies, ATLAS I and ATLAS II designed to compare the efficacy and safety of VIBATIV (10 mg/kg IV once daily) versus vancomycin (1 gm IV q 12hr) in adult patients with cSSSI caused by Gram-positive bacteria. A total of 1,867 patients were enrolled and treated, 719 of whom had infections with MRSA. In both of these studies, VIBATIV achieved its primary endpoint of non-inferiority relative to the standard of care, vancomycin. VIBATIV has not been studied in children.

Important Safety Information

Fetal Risk

Women of childbearing potential should have a serum pregnancy test prior to administration of VIBATIV. Avoid use of VIBATIV during pregnancy unless the potential benefit to the patient outweighs the potential risk to the fetus. Adverse developmental outcomes observed in three animal species at clinically relevant doses raise concerns about potential adverse developmental outcomes in humans. If not already pregnant, women of childbearing potential should use effective contraception during VIBATIV treatment.

Nephrotoxicity

New onset or worsening renal impairment occurred in patients who received VIBATIV. Renal adverse events were more likely to occur in patients with baseline comorbidities known to predispose patients to kidney dysfunction and in patients who received concomitant medications known to affect kidney function. Monitor renal function in all patients receiving VIBATIV prior to initiation of treatment, during treatment, and at the end of therapy. If renal function decreases, the benefit of continuing VIBATIV versus discontinuing and initiating therapy with an alternative agent should be assessed. Clinical cure rates in telavancin-treated patients were lower in patients with baseline CrCl less than or equal to 50 mL/min compared to those with CrCl greater than 50 mL/min. Consider these data when selecting antibacterial therapy for use in patients with baseline moderate/severe renal impairment.

Geriatric Use

Telavancin is substantially excreted by the kidney, and the risk of adverse reactions may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection in this age group.

Infusion Related Reactions

VIBATIV is a lipoglycopeptide antibacterial agent and should be administered over a period of 60 minutes to reduce the risk of infusion-related reactions. Rapid intravenous infusions of the glycopeptide class of antimicrobial agents can cause "Red-man Syndrome"-like reactions including: flushing of the upper body, urticaria, pruritus, or rash.

Clostridium difficile-Associated Diarrhea

Clostridium difficile-associated diarrhea (CDAD) has been reported with nearly all antibacterial agents and may range in severity from mild diarrhea to fatal colitis. CDAD must be considered in all patients who present with diarrhea following antibiotic use.

Development of Drug Resistant Bacteria

Prescribing VIBATIV in the absence of a proven or strongly suspected bacterial infection is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria. As with other antibacterial drugs, use of VIBATIV may result in overgrowth of nonsusceptible organisms, including fungi.

QTc Prolongation

Caution is warranted when prescribing VIBATIV to patients taking drugs known to prolong the QT interval. In a study involving healthy volunteers, VIBATIV prolonged the QTc interval. Use of VIBATIV should be avoided in patients with congenital long QT syndrome, known prolongation of the QTc interval, uncompensated heart failure, or severe left ventricular hypertrophy.

Coagulation Test Interference

VIBATIV does not interfere with coagulation, but does interfere with certain tests used to monitor coagulation such as prothrombin time, international normalized ratio, activated partial thromboplastin time, activated clotting time, and coagulation based factor Xa tests. Blood samples for these coagulation tests should be collected as close as possible prior to a patient's next dose of VIBATIV.

Adverse Reactions

The most common adverse reactions (greater than or equal to 10% of patients treated with VIBATIV) observed in the Phase III cSSSI clinical trials were taste disturbance, nausea, vomiting, and foamy urine.

In the Phase III cSSSI clinical trials, serious adverse events were reported in 7% of patients treated with VIBATIV and most commonly included renal, respiratory, or cardiac events. Serious adverse events were reported in 5% of vancomycin-treated patients, and most commonly included cardiac, respiratory, or infectious events.

Source
Theravance, Inc.