Durata Therapeutics, established in 2009, is a clinical development stage pharmaceutical company which focuses on the treatment of infectious diseases. The company acquired dalbavancin, a long-acting semisynthetic lipoglycopeptide antibiotic, from Pfizer in December 2009. Durata has initiated two Phase III studies of dalbavancin for intravenous treatment of acute bacterial skin and skin structure infections. In October of 2014 Durata was acquired by Actavis for about $675 million. Wikipedia.
Jones R.N.,JMI Laboratories |
Farrell D.J.,JMI Laboratories |
Flamm R.K.,JMI Laboratories |
Sader H.S.,JMI Laboratories |
And 2 more authors.
Diagnostic Microbiology and Infectious Disease | Year: 2015
Dalbavancin (DAL) represents a recently approved addition for the treatment of acute bacterial skin and skin structure infections (ABSSSIs). Newly released antimicrobial agents are rarely found on commercial susceptibility testing devices, and surrogate testing may be an option for clinical microbiology laboratories. A total of 33,688 Staphylococcus aureus, 2800 viridans group streptococci (VGS), and 5722 β-hemolytic streptococci (BHS) were included in this cross-susceptibility (DAL versus vancomycin [VAN]) analysis as well as 4576 coagulase-negative staphylococci and 6515 enterococci (nonindicated species groups). Isolates were collected as part of the SENTRY Antimicrobial Surveillance Program for the United States (USA) and Europe (2011-2013). Susceptibility testing followed CLSI (M07-A9 and M100-S24) methods. USA Food and Drug Administration (DAL) and CLSI (VAN) breakpoint criteria were used for correlations between DAL and VAN susceptibility results. A categorical agreement (CA; susceptible) rate of 99.9% was observed between DAL and VAN when testing S. aureus. Only 48 (0.14%) very major (false-susceptible) errors were noted against VAN-susceptible isolates that displayed a DAL-nonsusceptible (MIC, 0.25 or 0.5. μg/mL) phenotype. When susceptible MIC correlations were analyzed against indicated BHS species (Streptococcus agalactiae and Streptococcus pyogenes), an overall CA rate of 97.7-100.0% was obtained. Complete (100.0%) CA was documented for S. pyogenes, as well as against all VGS isolates, including the indicated Streptococcus anginosus group (758 strains). In conclusion, high susceptible CA rates between DAL and VAN were observed when testing a contemporary collection of indicated clinical isolates found in ABSSSI. VAN-susceptible isolates can be inferred to be inhibited by DAL (97.7-100.0%) at the regulatory agency-approved susceptible interpretive breakpoint of ≤0.12. μg/mL. © 2015 Elsevier Inc.
Dunne M.W.,Durata Therapeutics |
Zhou M.,iCardiac Technologies |
Darpo B.,iCardiac Technologies |
Darpo B.,Karolinska Institutet
International Journal of Antimicrobial Agents | Year: 2015
Two hundred healthy subjects were enrolled in a randomised, partially double-blinded, single-centre, parallel design thorough QT study to demonstrate that dalbavancin had no clinical effect on the 12-lead ECG QTc. Fifty patients in each group received either dalbavancin 1000 mg intravenous (i.v.), dalbavancin 1500 mg i.v. or placebo i.v., each infused over 30 min, or 400 mg oral moxifloxacin. Ten replicate 12-lead ECGs were extracted at pre-defined time points before and up to 24 h post dosing and at corresponding time points during baseline. Dalbavancin did not have an effect on the QTcF interval, and an effect exceeding 10 ms could be excluded at all time points after a single i.v. dose of 1000 mg and 1500 mg. The largest placebo-corrected change-from-baseline QTcF (ΔΔQTcF) was 1.5 ms in the 1000 mg dalbavancin group at 6 h and 0.2 ms in the 1500 mg group at 24 h. A small concentration-dependent effect of dalbavancin on ΔΔQTcF was identified with an estimated negative population slope of -0.0051 ms per μg/mL. Assay sensitivity was demonstrated by the effect of 400 mg moxifloxacin, which peaked at 2 h at ΔΔQTcF of 12.9 ms, with the lower bound of the 90% CI of the effect exceeding 5 ms at all three pre-defined time points. Dalbavancin did not exert a relevant effect on heart rate or PR or QRS intervals. Dalbavancin in i.v. doses up to 1500 mg did not prolong the QTc interval and had no effect on heart rate or PR and QRS intervals. © 2015 The Authors. Published by Elsevier B.V. on behalf of International Society of Chemotherapy.
Geli P.,Center for Disease Dynamics |
Laxminarayan R.,Center for Disease Dynamics |
Laxminarayan R.,Princeton Environmental Institute |
Dunne M.,Durata Therapeutics |
And 2 more authors.
PLoS ONE | Year: 2012
Historically, antibiotic treatment guidelines have aimed to maximize treatment efficacy and minimize toxicity, but have not considered the evolution of antibiotic resistance. Optimizing the duration and dosing of treatment to minimize the duration of symptomatic infection and selection pressure for resistance simultaneously has the potential to extend the useful therapeutic life of these valuable life-saving drugs without compromising the interests of individual patients. Here, using mathematical models, we explore the theoretical basis for shorter durations of treatment courses, including a range of ecological dynamics of bacteria that cause infections or colonize hosts as commensals. We find that immunity is an important mediating factor in determining the need for long duration of treatment. When immunity to infection is expected, shorter durations that reduce the selection for resistance without interfering with successful clinical outcome are likely to be supported. Adjusting drug treatment strategies to account for the impact of the differences in the ecological niche occupied by commensal flora relative to invasive bacteria could be effective in delaying the spread of bacterial resistance. © 2012 Geli et al.
Bradley J.S.,University of California at San Diego |
Puttagunta S.,Durata Therapeutics |
Rubino C.M.,State University of New York at Buffalo |
Blumer J.L.,University of Toledo |
And 2 more authors.
Pediatric Infectious Disease Journal | Year: 2015
Background: Dalbavancin is a lipoglycopeptide antibiotic with Gram-positive activity and novel pharmacokinetic (PK) properties that result in a prolonged terminal half-life of 15.5 days in adults. Once weekly dosing in adults in phase 3 studies of complicated skin and skin structure infections documented dalbavancin exposures associated with clinical and microbiologic efficacy. PK properties have not been examined in children. The primary objective of this open-label, multicenter single-dose phase 1 study was to characterize the PK of dalbavancin in hospitalized pediatric subjects 12-17 years of age. Methods: A single dose of 1000 mg of dalbavancin (the standard adult dose) was administered as a 30-minute intravenous infusion to subjects weighing 60 kg or greater and 15 mg/kg for subjects weighing <60 kg. A noncompartmental PK analysis was performed. Results: The apparent terminal t1/2 was approximately 9 days and was similar for dalbavancin dosages of 1000 mg and 15 mg/kg. Median dalbavancin plasma exposures (Cmax and AUCinf) when administered as 1000 mg to subjects weighing 60 kg or greater were similar to those when dalbavancin was administered at 15 mg/kg to subjects weighing <60 kg and slightly lower than exposures in adults given 1000 mg in prior PK and treatment studies. Single dose dalbavancin was well tolerated. Conclusions: Given dalbavancin exposures documented in children 12-17 years of age, and recognized dose proportionality, appropriate dosing can be modeled for pediatric phase 3 trials in acute bacterial skin and skin structure infections, to achieve the same exposure that is reported to be safe and effective in adults. © 2015 Wolters Kluwer Health, Inc.
News Article | January 27, 2015
President Barack Obama wants to spend $1.2 billion on the fight against antibiotic-resistant bacteria in the coming fiscal year, nearly doubling the nation's previous efforts. The proposal, a facet of the president's coming budget request, would put $650 million in the hands of the National Institutes of Health to fund the development of new anti-infective treatments and the launch of a large-scale study designed to better understand the evolution of drug resistance, the White House said. Another $47 million would go to the FDA to help speed along the review and approval of new treatments, and $280 million would fund the Centers for Disease Control and Prevention's efforts to keep tabs on outbreaks. The rest would be split among the Agriculture, Veterans Affairs and Defense departments. Drug-resistant bacteria lead to about 2 million illnesses and 23,000 deaths in the U.S. each year, according to the White House, and president's fiscal 2016 request would help "combat and prevent antibiotic resistance that will lead to critical new developments that could fundamentally transform how public health prevents the transmission and emergence of antibiotic-resistant infections," the administration said in a statement. Obama's embrace of antibiotic R&D comes alongside a complementary effort from some of the world's largest drugmakers, which, after years of inattention to the field, have kick-started development programs targeting deadly superbugs. Roche ($RHHBY) has struck a series of high-dollar deals to build its pipeline of anti-infectives, while the bottom-line conscious Actavis ($ACT), recognizing an opportunity, put up $675 million for antibiotic specialist Durata Therapeutics. Late last year, Merck ($MRK) made a splash in the space by agreeing to pay $9.5 billion Cubist Pharmaceuticals and its wide pipeline of critical care treatments. The White House's disclosure provides another clue that Obama is prioritizing research funding in his latest budget request, slated for release Feb. 2. During his State of the Union address last week, the president unveiled vague plans for a Precision Medicine Initiative, talking up the potential of molecularly targeted therapies and saying "the country that eliminated polio and mapped the human genome" is poised to lead a new era of medicine. Obama didn't attach any dollar figures to the effort, but many expect it to emulate the planned $4.5 billion BRAIN Initiative, a 2013 initiative through which NIH hands out grants each year with the goal of better understanding neuroscience. Related Articles: Roche inks a $750M antibiotics deal as it re-embraces the field Obama puts personalized medicine in the spotlight with a primetime pitch Merck splashes into antibiotics with $9.5B Cubist deal