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Durata Therapeutics Presents New Data for DALVANCE(TM) at IDWeek 2014(TM)

CHICAGO, Oct. 10, 2014 (GLOBE NEWSWIRE) -- Durata Therapeutics (Nasdaq: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 Studiesi

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 Infectionsii

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 Proceduresiii

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 Programiv

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 Programv

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.

ABOUT DURATA THERAPEUTICS

Durata Therapeutics is a pharmaceutical company focused on the development and commercialization of novel therapeutics for patients with infectious diseases and acute illnesses.

ABOUT DALVANCE

DALVANCE is a second generation, semi-synthetic lipoglycopeptide, which consists of a lipophilic side-chain added to an enhanced glycopeptide backbone. DALVANCE is the first and only IV antibiotic approved for the treatment of ABSSSI with a two-dose regimen of 1000 mg followed one week later by 500 mg, each administered over 30 minutes. DALVANCE demonstrates bactericidal activity in vitro against a range of Gram-positive bacteria, such as Staphylococcus aureus (including methicillin-resistant, also known as MRSA, strains) and Streptococcus pyogenes, as well as certain other streptococcal species.

IMPORTANT SAFETY INFORMATION

CONTRAINDICATIONS

DALVANCE is contraindicated in patients with known hypersensitivity to dalbavancin.

WARNINGS and PRECAUTIONS

Serious hypersensitivity (anaphylactic) and skin reactions have been reported with glycopeptide antibacterial agents, including DALVANCE; exercise caution in patients with known hypersensitivity to glycopeptides.

Rapid intravenous infusion of glycopeptide antibacterial agents can cause reactions, including flushing of the upper body, urticaria, pruritus and rash.

ALT elevations with DALVANCE treatment were reported in clinical trials.

Clostridium difficile-associated diarrhea (CDAD) has been reported with nearly all systemic antibacterial agents, including DALVANCE. Evaluate if diarrhea occurs.

ADVERSE REACTIONS

The most common adverse reactions in patients treated with DALVANCE were nausea (5.5%), headache (4.7%), and diarrhea (4.4%).

USE IN SPECIFIC POPULATIONS

In patients with renal impairment whose known creatinine clearance is less than 30 mL/min and who are not receiving regularly scheduled hemodialysis, the recommended two-dose regimen for DALVANCE is 750 mg followed one week later by 375 mg. No dosage adjustment is recommended for patients receiving regularly scheduled hemodialysis, and DALVANCE can be administered without regard to the timing of hemodialysis.

FORWARD-LOOKING STATEMENTS

Any statements in this press release about Durata's future expectations, plans and prospects constitute forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995, as amended. Actual results may differ materially from those indicated by such forward-looking statements. Durata anticipates that subsequent events and developments will cause its views to change. However, while Durata may elect to update these forward-looking statements at some point in the future, Durata specifically disclaims any obligation to do so.

REFERENCES

i Puttagunta S et al. Dalbavancin Versus Vancomycin for the Treatment of Acute Bacterial Skin and Skin Structure Infections (ABSSSI): A Subanalysis from the DISCOVER Studies. IDWeek Poster #266 (2014).

ii Dunne M, Puttagunta S et al.Dalbavancin for the Treatment of Streptococcal Skin Infections. IDWeek Poster #267 (2014).

iii Baldassarre J, et al. Pharmacokinetics of Dalbavancin (DAL) in Bone and Associated Tissues in Patients Undergoing Orthopedic Surgical Procedures. IDWeek Poster #398 (2014).

iv Puttagunta S et al. Outcomes of Acute Bacterial Skin and Skin Structure Infections (ABSSSI) by Vancomycin Dosing Regimen and Vancomycin Trough Serum Concentrations in the DISCOVER Program. IDWeek Poster #675 (2014).

v Dunne M, Puttagunta S et al. ASO and DNase Titers in Patients with Streptococcal Skin Infections in the Dalbavancin DISCOVER Program. IDWeek Poster #1345 (2014).

CONTACT: Allison Wey Durata Therapeutics, Inc. Vice President, Investor Relations and Public Affairs (312) 219-7017 awey@duratatherapeutics.com

Source:Durata Therapeutics, Inc.