Durata Therapeutics DRTX
today announced a summary of presentation data from its recently launched
product, DALVANCE™ (dalbavancin) for injection. The data were presented in
five posters at IDWeek 2014, which took place from October 8-11, 2014 in
Philadelphia, PA. Among the findings, a study of pharmacokinetic activity in
bone and associated tissues demonstrated that dalbavancin accumulates in bone
and supports further study in patients with osteomyelitis and prosthetic joint
infections. A separate analysis showed patients with ABSSSI who were treated
with dalbavancin had similar clinical success rates to those treated with IV
vancomycin alone, as well as a tendency to have fewer adverse events and less
nephrotoxicity compared to patients who received IV vancomycin for ≥10 days.
An examination of ASO and DNase-B titers in patients with streptococcal skin
infections in the dalbavancin DISCOVER program was also presented.
"Our data provides additional insight into the activity of dalbavancin
relative to vancomycin in the treatment of patients with ABSSSI, including
those infections associated with streptococcal disease," said Durata
Therapeutics Chief Medical Officer Michael Dunne, M.D. "Our studies also help
to support our commitment to understand the potential contribution of
dalbavancin to the treatment of other serious bacterial infections for which a
patient-oriented clinical solution is demanded, such as those with
osteomyelitis and joint infections."
Poster # 266: Dalbavancin Versus Vancomycin for the Treatment of Acute
Bacterial Skin and Skin Structure Infections (ABSSSI): A Subanalysis from the
DISCOVER Studies^i
This sub analysis compared the efficacy and safety outcomes of patients
enrolled in two prospective phase 3 ABSSSI clinical trials of dalbavancin
(DAL) versus vancomycin who only received study drug intravenously, with no
switch to oral therapy, for a total duration of 10-14 days. Data from the two
pivotal Phase 3 ABSSSI studies was pooled. Subset analyses were performed for
patients in both treatment groups who were not switched to oral study drug
therapy and received only IV vancomycin or placebo for the protocol specified
duration of treatment (10-14 days) and who received dalbavancin for greater
than 14 days. The study found that:
* Adult patients with ABSSSI treated with dalbavancin had similar clinical
success rates to those treated with IV vancomycin alone. Compared to
patients receiving dalbavancin, patients who received IV vancomycin for
≥10 days had a tendency to have more adverse events and more
nephrotoxicity.
Poster # 267: Dalbavancin for the Treatment of Streptococcal Skin
Infections^ii
Streptococci are a known cause of complicated skin and soft tissue infections
(cSSTI). Dalbavancin, a lipoglycopeptide antibiotic, has been studied in three
global phase 3 randomized, double-blind, controlled trials for the treatment
of acute bacterial skin and skin structure infections (ABSSSI) and cSSTI. The
objective of this analysis was to evaluate outcomes for patients with
streptococcal skin infections enrolled in the three global trials. Patients
enrolled in the three phase 3 ABSSSI/cSSTI trials with baseline cultures
positive for streptococcal species were identified. In these trials,
dalbavancin, 1 g IV on day 1 followed by 500mg IV on day 8 was compared to
either IV vancomycin or IV linezolid with an option to switch to oral
linezolid. The MIC distribution of streptococcal isolates and clinical
outcomes for patients with streptococcal skin infections were determined. The
study found that:
* Streptococcal infections were associated with a greater degree of
inflammation, as defined by larger areas of erythema and supported by
greater elevations in WBC and CRP. Data from the clinical trial program
confirmed the in vitro activity of dalbavancin against strains of
streptococci. Patients with streptococcal skin infections treated with
dalbavancin had similar clinical success rates at Day 14 and Day 28 to
those treated with comparator antibiotics. The analysis concluded that
vancomycin should be considered for use as a surrogate for in vitro
dalbavancin susceptibility testing for streptococci.
Poster # 398: Pharmacokinetics of Dalbavancin (DAL) in Bone and Associated
Tissues in Patients Undergoing Orthopedic Surgical Procedures^iii
Osteomyelitis (OM) is a serious infection requiring prolonged antimicrobial
therapy. Dalbavancin (DAL) may be an ideal antimicrobial agent for OM based on
its potent activity against S. aureus, and a long terminal half-life. Adults
scheduled for joint surgery (N = 31) were administered 1 g of DAL infused over
30 minutes prior to scheduled surgery. Patients were assigned to one of six
cohorts and had serial plasma PK samples collected up to 45 days post-dose
plus one bone PK sample collected at 12, 24, 72, 168, 240 or 336 hours
post-dose. Samples were analyzed for DAL in plasma, synovial fluid, skin,
cartilage and bone. A population PK model was fit to plasma and bone PK data
and covariate analysis was performed. Allometry was used to determine the
total amount of bone tissue and to estimate the amount of DAL in bone. The
study found that:
* Concentrations of dalbavancin in bone were well above the MBC for S.
aureus at 14 days post-dose. Adequate concentrations of dalbavancin were
also detected in synovium and synovial fluid. The analysis concluded that
based on its potency and long half-life, and concentrations reached in
relevant tissues, dalbavancin may be a useful therapeutic option for bone
and joint infections and deserves further clinical investigation.
Poster # 675: Outcomes of Acute Bacterial Skin and Skin Structure Infections
(ABSSSI) by Vancomycin Dosing Regimen and Vancomycin Trough Serum
Concentrations in the DISCOVER Program^iv
Dalbavancin is a lipoglycopeptide antibiotic with activity against
Gram-positive pathogens and a long half-life allowing for weekly dosing.
DISCOVER 1 and 2 were identically designed clinical trials of dalbavancin
versus vancomycin (VAN) with an option to switch to oral linezolid for the
treatment of ABSSSI. Outcomes were evaluated in adult patients with ABSSSI
treated with VAN by the dosing regimen utilized and the serum trough
concentrations measured. . Both trials were double-blind, double dummy,
pharmacist-unblinded randomized trials in which patients with ABSSSI were
randomized to receive dalbavancin 1g IV on Day 1 and 500 mg IV on Day 8 or VAN
1g (or 15mg/kg) IV every 12 hours (q12h) for at least three days with an
option to switch to oral linezolid 600 mg q12h to complete 10-14 days of
therapy. The primary endpoint was measured at 48-72 hours of therapy with
success requiring cessation of spread of the infection and absence of fever.
Secondary endpoints included clinical status at the end of therapy (EOT).
Outcomes by fixed versus weight-based dosing regimens of VAN and outcomes by
serum VAN trough concentrations were analyzed. The study found that:
* Clinical response rates for patients with ABSSSI were similar in patients
treated with a fixed-dose regimen or weight-based dosing regimen of
vancomycin. No association was observed between serum vancomycin trough
concentrations and efficacy outcomes at the 48-72 hour time point or at
EOT.
Poster # 1345: ASO and DNase Titers in Patients with Streptococcal Skin
Infections in the Dalbavancin DISCOVER Program^v
Elevated values of anti-Streptolysin O (ASO) and DNase-B antibody titers are
known to be consistent with antecedent group A streptococcal infections,
especially acute streptococcal pharyngitis, acute rheumatic fever or acute
glomerulonephritis, but not much is known about their association with
streptococcal skin infections. This analysis evaluated the presence of
elevated ASO/DNase-B titers in patients enrolled in two global phase 3
clinical trials comparing dalbavancin alone to vancomycin/linezolid for the
treatment of adult patients with acute bacterial skin and skin structure
infections (ABSSSI). Cultures obtained at a local laboratory at baseline were
sent to a central laboratory for species identification. ASO and DNase-B
titers were measured at baseline and Day 28. ASO titers were considered
elevated if there was a four-fold increase from baseline or if the titer was
>200 kIU/L at any time. The study found that:
* A higher proportion of patients with documented streptococcal skin
infections had elevated ASO and/or DNase-B titers than patients who did
not have streptococci isolated from cultures at baseline (ABSSSI patients
with an elevated ASO and DNase titer are more likely to have a
streptococcal etiology for their infection). Additionally, patients with
elevated ASO and DNase-B titers have a more severe clinical presentation
of their ABSSSI and a lower clinical success rate.
Copies of these posters are available on Durata's website: www.duratatx.com.
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