Durata Therapeutics Presents New Comprehensive Review of the Efficacy and
Safety Data of Dalbavancin and New In Vitro Findings at IDWeek 2013(TM)
SAN FRANCISCO, Oct. 2, 2013 (GLOBE NEWSWIRE) -- Durata Therapeutics, Inc.
(Nasdaq:DRTX) today announced a comprehensive review of the efficacy, safety
and microbiology data of the company's lead product candidate, dalbavancin,
for the treatment of patients with acute bacterial skin and skin structure
infections (ABSSSI). The data is being presented in six posters at this year's
IDWeek 2013™, held in San Francisco, Calif., October 2-6, 2013. Among the
findings, an integrated analysis of two Phase 3 clinical studies (DISCOVER 1
and 2) showed dalbavancin met its primary and secondary endpoints of early
response, measured at 48 to 72 hours of therapy, as well as clinical success
at the end of treatment. Sensitivity analyses for both timepoints were also
included.^i A separate analysis showed that patients achieving cessation of
spread of the lesion after 72 hours of antibiotic treatment with dalbavancin
have a greater than 90 percent chance of being cured at the end of
treatment.^ii A pooled summary analysis of the safety profile of dalbavancin
based on the Phase 2 and 3 clinical program also found it to be generally
well-tolerated and to have a similar safety profile to comparators with fewer
adverse events.^iii Examination of patients with baseline Gram-positive
bacteremia enrolled in the dalbavancin clinical development program as well as
in vitro activity against methicillin-resistant Staphylococcus aureus (MRSA)
and Neisseria gonorrhoeae were also presented.
"The data show that dalbavancin has the potential to be an efficacious and
well-tolerated treatment option for patients with ABSSSI," said Durata
Therapeutics Chief Medical Officer Michael Dunne, M.D. "Our studies were
designed to meet the new standards required by regulatory authorities for
antibiotic development in the United States and European Union and support our
New Drug Application submission to the Food and Drug Administration late last
Dalbavancin is a novel antibacterial under investigation for the treatment of
ABSSSI caused by susceptible Gram-positive microorganisms, such as S. aureus
(including MRSA and other multi-drug resistant strains) and Streptococcus
pyogenes, as well as certain other streptococcal species. Dalbavancin is
bactericidal against Gram-positive bacteria and is administered with a
once-weekly dosage regimen of 1000 mg on Day 1 and 500 mg on Day 8, over 30
minutes by intravenous infusion.
Copies of the following posters will be available on Durata Therapeutics'
Poster # 1339: An Integrated Analysis of the Efficacy of Dalbavancin for the
Treatment of Acute Bacterial Skin and Skin Structure Infections (ABSSSI) in
the DISCOVER Program^i (Date: October 5, 2013)
Data were presented from an integrated analysis of the efficacy results from
the DISCOVER ("Dalbavancin for Infections of the Skin COmpared to Vancomycin
at an Early Response") program and found that dalbavancin is non-inferior to
the comparator regimen at both an early timepoint and at the end of therapy.
The DISCOVER program includes two Phase 3 identically designed multicenter,
double-blind, randomized clinical trials of more than 1,300 adult patients
with ABSSSI from the United States, Europe, Asia and South Africa. Patients
were treated for two weeks either with intravenous dalbavancin once weekly
(1000 mg on Day 1 followed by 500 mg on Day 8) or with intravenous vancomycin
(1000 mg or 15 mg/kg every 12 hours) with the option to switch to oral
linezolid after three days. Primary endpoints from the DISCOVER trials were
cessation of spread of the erythema associated with the lesion and resolution
of fever measured at 48-72 hours per FDA requirements. While a secondary
endpoint for FDA, clinical success at end of treatment is the expected primary
endpoint for regulatory review in Europe. Examining both endpoints provides
clinicians with correlation between the early and late findings.
The integrated efficacy analysis found that:
*Dalbavancin had similar efficacy rates relative to the comparator regimen
in demonstrating the combination of cessation of lesion spread and absence
of fever 48-72 hours following initiation of treatment
*Success rates at the Day 14 end of treatment and the Day 28 follow up
visit were similar in both treatment groups
Poster # 1340: Concordance of Clinical Response at 48-72 Hours after
Initiation of Therapy and End of Treatment (EOT) in Patients with Acute
Bacterial Skin and Skin Structure Infection (ABSSSI) in the DISCOVER
Studies^ii (Date: October 5, 2013)
An additional analysis of the DISCOVER clinical trials examined the
concordance of study endpoints (i.e., clinical response at 48-72 hours after
initiation of therapy as well as at the end of treatment) and found that the
majority of early responders were ultimately cured. Specifically, the analysis
*The majority (945/1,046, 90.3%) of patients who responded favorably to
treatment with dalbavancin by 48 to 72 hours were ultimately cured by the
end of treatment
*Most (129/182, 70.9%) patients who were non-responders on Day 3 were also
subsequently cured by the end of treatment
*Patients who do not achieve cessation of lesion spread at 72 hours alone
and have worsening pain have an 80 percent chance of ultimately failing
"The early assessment timepoint recommended by the FDA was put in place to
guide antibiotic drug development for ABSSSI," said Mark Wilcox, M.D., Head of
Microbiology, Leeds Teaching Hospitals and Professor of Medical Microbiology
at the University of Leeds, UK and an advisor to the DISCOVER clinical trial
program. "These data, however, may also give physicians confidence at an early
timepoint that could help identify patients who could ultimately be cured and
those who might fail."
Poster # 1343: Clearance of Staphylococcus aureus Bacteremia in Patients
Treated with Dalbavancin^iv (Date: October 5, 2013)
Data collected from three Phase 3 trials with skin and skin structure
infections and one Phase 2 catheter-related infection study support the use of
dalbavancin in patients with skin infections who also have a bacteremia at
baseline. Blood cultures were drawn at baseline from two anatomical sites and
not through an existing intravenous line. If positive at baseline, blood
cultures were to be repeated every 48-72 hours until negative. Comparators
included vancomycin and linezolid. The study found that:
*All patients in the dalbavancin group with baseline Gram-positive
bacteremia, including those with S. aureus, (n=71) who had follow-up blood
cultures available (n=61), had documented clearance of their bacteremia
and clinical outcome rates at end of treatment similar to comparators
Poster # 1334: An Analysis of the Safety Profile of Dalbavancin from the Phase
2/3 Clinical Program^iii (Date: October 5, 2013)
In the most comprehensive review of safety data from dalbavancin's clinical
program to-date, including Phase 2 and Phase 3 clinical trials of more than
3,000 patients, data showed that dalbavancin is safe and generally
well-tolerated relative to comparator agents used for treatment of skin
infections. A substantial proportion of patients were enrolled from the United
States (64.3%), younger than age 65 (82.4%), white (78.1%) and overweight
(71.6%) and should reflect the intended population of patients with these
types of infections in clinical practice. The integrated safety analysis found
*The percentage of subjects with treatment emergent adverse events, the
frequency of treatment emergent adverse events and the adverse event
burden experienced by patients in the dalbavancin group were lower than
those in the comparator treatment group
*The duration and time to onset of treatment emergent adverse events was
similar in the dalbavancin and comparator groups
*The most commonly reported adverse events for dalbavancin or the
comparator respectively, included nausea (2.8% vs. 3.3%), diarrhea (2.5%
vs. 3.7%), headache (1.5% vs. 1.6%), elevated gamma-glutamyl transferase
(1.1% vs. 1.0%), rash (1.0% vs. 1.1%), vomiting (1.0% vs. 0.9%) and
pruritus (0.6% vs. 1.9%)
Poster # 1338: Microbiologic Analyses of Target Pathogens Identified in the
Dalbavancin DISCOVER Program^v (Date: October 5, 2013)
Target pathogens isolated at baseline from the DISCOVER clinical trials were
tested in vitro for susceptibility to a panel of antibiotics, including
dalbavancin. The study demonstrated the potent in vitro activity of
dalbavancin against key Gram-positive pathogens, including MRSA (n=273), MSSA
(n=396) and streptococci (n=151) causing ABSSSI. Specifically, the study found
*The MIC of dalbavancin for S. aureus, whether MRSA or MSSA, was less
than or equal to 0.06 µg/mL
*The MIC of dalbavancin for target streptococci was less than 0.06
Poster # 255: In Vitro Activity of Dalbavancin against Neisseria gonorrhoeae
and Development of a Broth Microdilution Method^vi (Date: October 3, 2013)
A study examined the in vitro activity of dalbavancin against a challenge set
of N. gonorrhoeae– declared an urgent threat by the Centers for Disease
Control and Prevention^vii – and found that the in vitro activity of
dalbavancin against N. gonorrhoeae by broth microdilution is an indication of
possible in vivo activity that will require further investigation. Given that
antibiotic susceptibility testing for dalbavancin is performed in broth,
efforts were made to explore methodologies to understand growth of N.
gonorrhoeae in broth rather than agar. Dalbavancin, ceftriaxone and
ciprofloxacin broth microdilution and agar dilution MIC results were obtained
for a set of 31 N. gonorrhoeae (11 susceptible strains including quality
control strain ATCC 49226 and 20 resistant strains) and quality control S.
aureus ATCC 29213. A modified gonococcus (GC) broth (substitution of glucose
instead of starch) + 0.002 percent polysorbate 80 was used for testing of
dalbavancin and GC broth was used for the two comparator agents. All MIC
plates were incubated in CO and results were read after 48 hours. The study
*Dalbavancin BMD MICs (48 hours in 5% CO) were 0.12-1 µg/mL with a MIC90
of 0.5 µg/mL
*The addition of 0.002% P-80 to modified GC broth provides N. gonorrhoeae
dalbavancin MIC results that are on average 3 dilutions lower compared to
*Further development to determine the optimal broth and incubation
conditions are necessary
This study was conducted by Dr. Laura Koeth, Laboratory Specialists, Inc., and
sponsored by a grant from Durata Therapeutics.
For the six month period of January to June 2010, a projected 9.2 million
patients were treated in U.S. hospitals for infections of any type, and nearly
17 percent of the diagnostic category presentations were for skin and skin
structure infections (SSSIs). Of these presentations for SSSI, approximately
74 percent were disease types included in ABSSSI.^viii This category of
infection increased by 176 percent from 1997 to 2009 in hospitalized
patients.^ix The majority of skin and soft tissue infections in hospitalized
patients are caused by Staphylococcus aureus and approximately 59 percent of
these infections are estimated to be caused by MRSA in the U.S.^x,xi Effective
early treatment of ABSSSI is critical to prevent wound expansion and to avoid
lengthy and costly hospital stays.^xii Failure to successfully treat ABSSSI
may result in hospital readmissions. Under the new health care reform laws,
hospitals may incur financial penalties for preventable hospital readmissions,
including unresolved infections.
About N. Gonorrhoeae
Neisseria gonorrhoeae causes gonorrhea, a sexually transmitted disease that
can result in discharge and inflammation at the urethra, cervix, pharynx or
rectum. Gonorrhea is the second most commonly reported notifiable infection in
the United States and is easily transmitted. N. gonorrhoeae is showing
resistance to the antibiotics typically used to treat it. The CDC estimates
there are at least 246,000 cases of drug-resistant N. gonorrhoeae each year,
and recently assigned it to an urgent hazard level in its report "Antibiotic
resistance threats in the United States, 2013."^vii
Dalbavancin is a second generation, semi-synthetic lipoglycopeptide, which
consists of lipophilic side-chains attached to glycopeptides. When compared to
vancomycin, dalbavancin has a longer half-life resulting in a duration of
antibacterial activity of 5-7 days per dose.^xiii If approved, dalbavancin
would be the first drug for ABSSSI requiring a once-weekly dosage regimen of
1000 mg on Day 1 and 500 mg on Day 8, over 30 minutes by intravenous infusion.
This may allow for the treatment of patients with ABSSSI in both inpatient and
outpatient settings—potentially shortening the length of patient hospital
stays, or in some cases, eliminating hospital admissions altogether.^xiv
Ultimately, this may lower the overall cost of care for these patients.
About Durata Therapeutics, Inc.
Durata Therapeutics is a pharmaceutical company focused on the development and
commercialization of novel therapeutics for patients with infectious diseases
and acute illnesses. Durata has completed two global Phase 3 clinical trials
with its lead product candidate, dalbavancin, under investigation for the
treatment of patients with acute bacterial skin and skin structure infections
caused by susceptible Gram-positive bacteria.
About IDWeek 2013™
IDWeek 2013™ is an annual meeting of the Infectious Diseases Society of
America (IDSA), the Society for Healthcare Epidemiology of America (SHEA), the
HIV Medicine Association (HIVMA) and the Pediatric Infectious Diseases Society
(PIDS). With the theme "Advancing Science, Improving Care," IDWeek features
the latest science and bench-to-bedside approaches in prevention, diagnosis,
treatment, and epidemiology of infectious diseases, including HIV, across the
lifespan. IDWeek 2013 takes place October 2-6 at the Moscone Center in San
Francisco, California. The full name of the meeting is IDWeek 2013™. For more
information, visit www.idweek.org.
Statements contained in this press release contain forward-looking statements
that involve substantial risks and uncertainties. All statements, other than
statements of historical facts, contained in this press release, including
statements regarding our strategy, future operations, future financial
position, future revenues, projected costs, prospects, plans and objectives of
management, are forward-looking statements. The words "anticipate," "believe,"
"estimate," "expect," "intend," "may," "plan," "predict," "project," "target,"
"potential," "will," "would," "could," "should," "continue," and similar
expressions are intended to identify forward-looking statements, although not
all forward-looking statements contain these identifying words.
Forward-looking statements in this press release include statements about the
potential FDA approval of dalbavancin and the impact of once-weekly dosing of
dalbavancin. Actual results may differ materially from those indicated by
these forward-looking statements as a result of various important factors,
including those discussed in the "Risk Factors" section of our most recent
quarterly report on Form 10-Q, which is on file with the SEC and is also
available on our website. In addition, any forward-looking statements
represent our views only as of today and should not be relied upon as
representing our views as of any subsequent date. While we may elect to update
these forward-looking statements at some point in the future, we specifically
disclaim any obligation to do so, even if our views change. Therefore, you
should not rely on these forward-looking statements as representing our views
as of any date subsequent to today.
i Wilcox M, Boucher H et al. An Integrated Analysis of the
Efficacy of Dalbavancin for the Treatment of Acute Bacterial Skin and Skin
Structure Infections (ABSSSI) in the DISCOVER Program. IDWeek Poster #1339
ii Dunne M, Puttagunta S et al.Concordance of Clinical Response
at 48-72 Hours after Initiation of Therapy and End of Treatment (EOT) in
Patients with Acute Bacterial Skin and Skin Structure Infection (ABSSSI) in
the DISCOVER Studies. IDWeek Poster #1340 (2013).
iii Dunne M, Das A et al. An Analysis of the Safety Profile of
Dalbavancin from the Phase 2/3 Clinical Program. IDWeek Poster #1334 (2013).
iv Dunne M, Puttagunta S et al. Clearance of Staphylococcus
aureus Bacteremia in Patients Treated with Dalbavancin. IDWeek Poster #1343
v Dunne M, Boucher H et al. Microbiologic Analyses of Target
Pathogens Identified in the Dalbavancin DISCOVER Program. IDWeek Poster
vi Koeth L, Fisher J. In vitro Activity of Dalbavancin against
Neisseria gonorrhoeae and Development of a Broth Microdilution Method.
IDWeek Poster #255 (2013).
vii Centers for Disease Control and Prevention. Antibiotic
Resistance Threats in the United States, 2013. (2013).
viii AMR Hospital Antibiotic Market Guide - Book 2: Diagnosis and
Surgery Reports, January 2010 – June 2010.
ix Giuliano C, Kale-Pradhan P, et al. Early Response of
Ceftaroline Fosamil in the Treatment of Soft-tissue Infections. Expert Rev
Clin Pharmacol. 5(5):509-512 (2012).
x Moet G, Jones R, et al. Contemporary causes of skin and soft
tissue infections in North America, Latin America and Europe: Report from
the SENTRY Antimicrobial Surveillance Program (1998-2004). Diagnostic
Microbiology and Infectious Disease. 57, 7-13 (2007).
xi Moran GJ, Krishnadasan A, Gorwitz RJ et al. EMERGEncy ID Net
Study Group. Methicillin-resistant S. aureus Infections Among Patients in
the Emergency Department. N. Engl. J. Med. 355(7), 666–674 (2006).
xii Parta M, M Goebel et al. Impact of an Assay That Enables
Rapid Determination of Staphylococcus Species and Their Drug Susceptibility
on the Treatment of Patients with Positive Blood Culture Results. Infect.
Control and Hospital Epidemiology. 31(10), 1043-1048 (2010).
xiii Durata DOF.
xiv Durata Therapeutics website. About dalbavancin.
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