Theravance Biopharma Enrolls First Patient in Phase 3 Registrational Study of Telavancin in Staphylococcus Aureus Bacteremia
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 Chief Executive Officer. "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
"Mortality rates for MRSA bacteremia range up to 30 percent despite currently available treatments," 3-6 stated
- 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 (ELF), alveolar macrophages (AM), 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
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 in patients with Staphylococcus aureus bacteremia, particularly when the infection is caused by MRSA. Mortality rates associated with Staphylococcus aureus bacteremia remain high, reported in the range of 20-30%.3-6 Mortality is higher among patients with MRSA infection.7,8
About VIBATIV® (telavancin)
VIBATIV was discovered internally 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 in vitro potency and a dual mechanism of action whereby telavancin both inhibits bacterial cell wall synthesis and disrupts bacterial cell membrane function. VIBATIV is approved in the U.S. for the treatment of adult patients with HABP/VABP when alternative treatments are not suitable and for cSSSI caused by susceptible isolates of Gram-positive bacteria, including Staphylococcus aureus, both methicillin-susceptible (MSSA) and methicillin-resistant (MRSA) strains.
Clinigen Group holds the commercial rights to market and distribute VIBATIV in
VIBATIV® Important Safety Information (U.S.)
Patients with pre-existing moderate/severe renal impairment (CrCl ≤ 50 mL/min) who were treated with VIBATIV for hospital-acquired bacterial pneumonia/ventilator-associated bacterial pneumonia had increased mortality observed versus vancomycin. Use of VIBATIV in patients with pre-existing moderate/severe renal impairment (CrCl ≤ 50 mL/min) should be considered only when the anticipated benefit to the patient outweighs the potential risk.
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.
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.
Intravenous unfractionated heparin sodium is contraindicated with VIBATIV administration due to artificially prolonged activated partial thromboplastin time (aPTT) test results for up to 18 hours after VIBATIV administration.
VIBATIV is contraindicated in patients with a known hypersensitivity to the drug.
Serious and potentially fatal hypersensitivity reactions, including anaphylactic reactions, may occur after first or subsequent doses. VIBATIV should be used with caution in patients with known hypersensitivity to vancomycin.
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.
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.
Most Common Adverse Reactions
The most common adverse reactions (greater than or equal to 10% of patients treated with VIBATIV) were diarrhea, taste disturbance, nausea, vomiting, and foamy urine.
Full Prescribing Information, including Boxed Warning and Medication Guide in the U.S., is available at www.VIBATIV.com.
The mission of
Our pipeline of internally discovered product candidates includes potential best-in-class opportunities in underserved markets in the acute care setting, representing multiple opportunities for value creation. VIBATIV® (telavancin), our first commercial product, is a once-daily dual-mechanism antibiotic approved in the U.S. and
With our successful drug discovery and development track record, commercial infrastructure, experienced management team and efficient corporate structure, we believe that we are well positioned to create value for our shareholders and make a difference in the lives of patients.
For more information, please visit www.theravance.com.
THERAVANCE®, the Cross/Star logo, MEDICINES THAT MAKE A DIFFERENCE® and VIBATIV® are registered trademarks of the
This press release contains certain "forward-looking" statements as that term is defined in the Private Securities Litigation Reform Act of 1995 regarding, among other things, statements relating to goals, plans, objectives and future events.
1 Lodise TP, Graves J, Evans A, Graffunder E, Helmecke M, Lomaestro BM, Stellrecht K. Relationship between vancomycin MIC and failure among patients with methicillin-resistant Staphylococcus aureus bacteremia treated with vancomycin. Antimicrob Agents Chemother. 2008;52(9):3315.
3 Whitby M, McLaws ML, Berry G. Risk of death from methicillin-resistant Staphylococcus aureus bacteraemia: a meta-analysis. Med J Aust.
4 Benfield T, Espersen F, Frimodt-Møller N,
5 Turnidge JD, Kotsanas D, Munckhof W, Roberts S, Bennett CM, Nimmo GR, Coombs GW, Murray RJ, Howden B, Johnson PD, Dowling K;
6 van Hal SJ, Jensen SO, Vaska VL, Espedido BA, Paterson DL, Gosbell IB. Predictors of mortality in Staphylococcus aureus bacteremia. Clin Microbiol Rev.
7 Marra AR, Edmond MB, Forbes BA, Wenzel RP, Bearman GM. Time to blood culture positivity as a predictor of clinical outcome of Staphylococcus aureus bloodstream infection. J Clin Microbiol. 2006;44(4):1342.
8 Cosgrove SE, Sakoulas G, Perencevich EN, et al. Comparison of mortality associated with methicillin-resistant and methicillin-susceptible Staphylococcus aureus bacteremia: a meta-analysis. Clin Infect Dis 2003;36:53-9.
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