Theravance Biopharma Reports Positive New Data from Multiple Studies of VIBATIV® (telavancin) at IDWeek™ 2018
Details from the two TOUR-related IDWeek presentations are as follows:
Researchers presented data reported for 159 patients captured in the TOUR study who were diagnosed with monomicrobial S. aureus infections with vancomycin MIC ≥ 1 µg/mL . Of these VIBATIV was used as a second-line or greater therapy in 77.4% of patients, with 44.0% having previously been treated with vancomycin. Among the 144 patients who had an outcome assessment at end of therapy with VIBATIV, a positive clinical response was reported for 77.1%, with 9.7% failing to respond to treatment and 13.2% having an indeterminate clinical outcome. The patients' most common infection types were complicated skin and skin structure infections (45.9%), bacteremia and endocarditis (20.1%), and osteomyelitis (15.7%). The median VIBATIV daily dose and duration of treatment were 8.5 mg/kg and 8 days, respectively.
MICs are a measure used to express in vitro activity of an antibiotic against a pathogen, with the greater the MIC, the less activity an antibiotic possesses against the pathogen. When a pathogen demonstrates vancomycin MIC ≥ 1 µg/mL, it suggests that the pathogen has relatively poor susceptibility to vancomycin. Among the 159 patients, 65.4% of patients had vancomycin MIC = 1 µg/mL; 2.5% had vancomycin MIC = 1.5 µg/mL, and 32.1% had vancomycin MIC = 2 µg/mL.
Of the 159 patients, 17 reported an adverse event, with 12 discontinuing treatment due to an adverse event. The most commonly occurring adverse event was renal failure (4.4%), which resolved in the majority of cases. Importantly, there were no new safety signals identified in this patient subset.
"As a clinician, it is critical that I have a trusted antibiotic option with excellent in vitro potency to turn to when I encounter S. aureus infections with reduced susceptibility to vancomycin. These data from TOUR highlight that VIBATIV should be considered one of those alternative treatment options in this era of rising vancomycin MICs in order to ensure patients are getting effective therapy," said
VIBATIV Treatment for Longer than 21 Days
Researchers presented data reported for 308 patients captured in the TOUR study who received VIBATIV therapy for longer than 21 days. Infection characteristics demonstrate the significant health challenges facing this subgroup of patients, with the majority of patients presenting with bone and joint infections (55.2%), including osteomyelitis, which are notoriously difficult to treat. In addition, 39.3% of patients had infections caused by methicillin-resistant S. aureus (MRSA), a pathogen that is resistant to several antibiotics. Of these patients, 76.3% were treated with VIBATIV as second-line or greater therapy, with 65.6% of patients treated as outpatients prior to starting VIBATIV therapy. The median VIBATIV daily dose and duration of treatment were 8.3 mg/kg and 38 days, respectively.
Among the group of 308 patients receiving VIBATIV therapy for longer than 21 days, 134 had their CrCl measured and recorded at baseline and end of VIBATIV therapy (EOT), allowing researchers to assess the impact of this prolonged VIBATIV treatment on their renal function. In comparing baseline and EOT CrCl measurements, researchers determined that renal function was unchanged for 68.7% these patients. Additionally, CrCl comparisons suggested improved renal function for 6.7% of patients and decreased renal function for 24.6% of patients.
CrCl is a standard measure used to assess and quantify renal function. These measures are typically categorized into ranges to provide a framework for assessing changes in renal function. In this study, CrCl measures were grouped as follows: ≤ 30mL/min; > 30-50 mL/min; > 50-80 mL/min; and > 80 mL/min. When comparing baseline and EOT CrCl, TOUR researchers considered a patient's CrCL, and thus renal function, to be unchanged if it remained in the same range grouping. Those patients whose EOT CrCl moved into a higher or lower CrCl range grouping from baseline, were considered to have renal function that changed.
Of the 308 patients, 36 reported an adverse event, with 18 discontinuing treatment due to an adverse event. The most commonly occurring adverse event was renal failure (8.1%), which resolved in the majority of cases. Importantly, there were no new safety signals identified in this patient subset.
"We are encouraged to see that prolonged treatment with VIBATIV led to no change in renal function for 68.7% of these very sick patients. It is also noteworthy that only 8.1% of the entire group of 308 patients receiving VIBATIV for longer than 21 days reported a renal adverse event, the majority of which resolved on their own," said
TOUR is a multi-center, observational study that enrolled 1,063 patients from 45 sites in the US. As a non-interventional study, all treatment decisions were at the discretion of the patient's healthcare provider. Study patients may have treatment initiated in either hospital-based settings or out-patient infusion sites. To qualify for enrollment in TOUR, patients must have received at least one dose of VIBATIV and meet specified inclusion criteria. By broadly collecting and examining real-world data related to VIBATIV treatment patterns, clinical effectiveness and safety outcomes in medical practice,
- Assisting in optimizing use in patients currently being treated with VIBATIV;
- Potentially highlighting subsets of patients that may be most appropriate for treatment with VIBATIV; and
- Illustrating current healthcare practitioner's patterns of VIBATIV use.
VIBATIV® was discovered internally in a research program dedicated to finding new antibiotics for serious infections due to Staphylococcus aureus(S. aureus) and other Gram-positive bacteria, including MRSA and MSSA. VIBATIV is a once-daily, injectable lipoglycopeptide antibiotic with in vitro potency, bactericidal activity within six hours, and penetration into target infection sites. The drug is approved in the U.S. for the treatment of adult patients with hospital-acquired and ventilator-associated bacterial pneumonia (HABP/VABP) caused by susceptible isolates of S. aureus when alternative treatments are not suitable. In addition, VIBATIV is approved in the U.S. for the treatment of adult patients with complicated skin & skin structure infections (cSSSI) caused by susceptible isolates of Gram-positive bacteria, including S. aureus, both methicillin-susceptible (MSSA) and methicillin-resistant (MRSA) strains. The product labeling also describes the use of VIBATIV in treating patients whose pneumonia or skin infection is complicated by concurrent bacteremia.
The product's proven efficacy against difficult-to-treat Gram-positive infections has been demonstrated in several large, multinational registrational studies, which involved one of the largest cohorts of patients with S. aureus infections studied to date. Importantly, these studies demonstrated significantly higher cure rates for VIBATIV as compared to vancomycin in HABP/VABP due to any single Gram-positive pathogen or S. aureus with vancomycin MIC ≥1 µg/mL. Additionally, there is extensive and well-documented evidence of the drug's in vitro potency and in vivo activity against a broad collection of Gram-positive bacterial pathogens, including those that are considered difficult-to-treat and multidrug-resistant.
VIBATIV is also approved for marketing in
VIBATIV®(telavancin)Important Safety Information
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.
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